Poonsakdi Ploypradith - Academia.edu (original) (raw)
Papers by Poonsakdi Ploypradith
Synlett
By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three ... more By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three steps. Subsequent Grignard/aryl lithium addition to the ketone yielded the corresponding tertiary alcohols that underwent stereoselective acid-catalyzed transannular cyclization to provide a cis-fused 5/5 bicyclic indanylindane framework exclusively. Subsequent stereoselective nucleophilic addition to the indanyl cation by hydride, water, or electron-rich aromatics furnished the 4b-aryltetrahydroindano[1,2-a]indenes in good to excellent yields (up to 92%) in the trans-C9–C9a form in up to a >99:1 diastereomeric ratio.
Chemistry - An Asian Journal, 2015
With the goaltoi mprove the aqueous solubility of lamellarins, the lactone ring in their skeleton... more With the goaltoi mprove the aqueous solubility of lamellarins, the lactone ring in their skeleton was replaced with al actam moiety in azalamellarins. However,t he reported synthetic route produced such derivatives in very low yields. Hence, this study focused on developing an efficient simplified total synthetic scheme that could furnish both azalamellarins and the parentl amellarins from the same pyrrole ester intermediates. Subsequent comparative profiling revealed that the introduced lactone-to-lactam replacement rendered these molecules less lipophilic, whereas their cancer cytotoxicity remained equipotent to that of the parentc ompounds. Interestingly,t heir inhibitory activity was significantly enhanced towards the multifaceted GSK-3b enzyme. Our results clearly demonstrate the therapeutic potential of this promising class of marine-derived natural products and justify their further development, especially into anticancer agents.
Chemistry, an Asian journal, 2015
Chemistry - An Asian Journal, 2015
Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-c... more Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-cycloalkylfused and 6-modified chromans could be prepared via ortho-quinone methides (o-QMs)/hetero-Diels-Alder (HDA) reactions of the appropriate precursors. The bromide at C6 served as a handle for introducing other substituents through palladium-catalyzed cross-coupling reactions and other functional-group transformations. Moderate to high yields (up to 80 %) and diastereoselectivities (up to > 99:1) could be obtained under [PtCl 4 ] catalysis. The preferred endo transition state during the cycloaddition reaction played an important role in governing the stereochemical outcomes at C2ÀC3ÀC4. The configurationally fixed E geometry of the bicyclic o-QMs influenced the cycloaddition reactions to favor the C2ÀC4 cis relationship.
Tetrahedron Letters, 2011
ABSTRACT A novel approach for the syntheses of lophocladines A and B has been developed. These co... more ABSTRACT A novel approach for the syntheses of lophocladines A and B has been developed. These compounds were prepared in 4-6 steps with moderate to excellent overall yields. The key step involved the nucleophilic substitution of 4-chloronicotinic acid with the carbanion generated from phenylacetonitrile. Subsequent reduction of the cyano group, lactamization and oxidation furnished lophocladine A in 50% yield over 4 steps. Further amination with various amines led to lophocladine B and its Cl analogues in good yields. In addition, the synthesized compounds were evaluated for their cytotoxicity against leukaemia cells.
![Research paper thumbnail of Pt(IV)-catalyzed generation and [4+2]-cycloaddition reactions of o-quinone methides](https://attachments.academia-assets.com/86680073/thumbnails/1.jpg)
](Tetrahedron, 2011
Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4... more Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4þ2]cycloaddition reactions with olefins catalyzed by PtCl 4 and AuCl 3 under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl 4 was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.
Organic Letters
p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found ... more p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found to be effective in cleaving aromatic ethers containing isopropyl, tert-butyl, allyl, and benzyl groups, as well as mono-, di-, and trimethoxylated benzyl groups, in moderate to excellent yields (54−95%). These protecting groups could be selectively deprotected when they were simultaneously present on the same or different aromatic rings in a substrate. Protecting groups are important tools in organic synthesis as they have found extensive use in many different areas of complex syntheses of natural products, biomolecules, and materials. 1 Crucial features of protecting groups are their ease of preparation and removal as well as their relative stability toward different reaction conditions. A number of moieties such as benzyl, isopropyl, tert-butyl, and mono-or polymethoxylated benzyl, among others, have been developed as protecting groups for both aliphatic and aromatic hydroxy functionalities. 2 Reaction conditions for preparing and removing these protecting groups have been investigated. 3 New reagents and reaction conditions have been continually developed for protecting and/or deprotecting purposes. 4 Current awareness and interest in green chemistry has prompted many research groups, including ours, to investi
Monatshefte für Chemie - Chemical Monthly, 2010
The common structural requirements for cytotoxicity of lamellarins against two human breast cance... more The common structural requirements for cytotoxicity of lamellarins against two human breast cancer cell lines were determined using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Twenty lamellarins were selected to serve as the training set, whereas another group of six compounds were used as the test set. The best CoMFA and CoMSIA models for both cell lines yielded satisfactory predictive ability with r cv 2 values in the range of 0.659-0.728. Additionally, the contour maps obtained from both the CoMFA and CoMSIA models agreed well with the experimental results and may be used in the design of more potent cytotoxic compounds for human breast cancers. Both analyses not only suggested structural requirements of various substituents around the lamellarin skeleton for their cytotoxic activity against both human breast cancer cell lines but also revealed the molecular basis for the differences between the saturated and unsaturated D-rings of the lamellarins.
The Journal of Organic Chemistry, 2009
2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the o... more 2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene under mild conditions (0 degrees C to rt). The corresponding chromans were obtained in moderate to excellent yields (42-97%) and in moderate to excellent diastereoselectivity (up to >99:1).
ChemMedChem, 2009
Twenty-two naturally occurring and three unnatural lamellarins were synthesized and evaluated for... more Twenty-two naturally occurring and three unnatural lamellarins were synthesized and evaluated for their cytotoxicities against cancer cells. Across eleven cancer cell lines derived from six different cancer types, the IC(50) values of these compounds ranged from sub-nanomolar (0.08 nM) to micromolar (>97.0 microM). About one-fourth (6/25) and one-half (11/25) of these lamellarins are more potent than the positive control, etoposide, against at least six different cell lines and three different cell types, respectively. In general, lamellarins D, X, epsilon, M, N, and dehydrolamellarin J are significantly more potent than the other lamellarins. The IC(50) values were used to perform structure-activity relationship (SAR) studies by comparing the cytotoxic activities of several pairs of lamellarin structures that differ in selected substitution patterns. Our results not only reveal the importance of specific hydroxylation or methoxylation patterns for the first time, but also confirm prior findings and clarify some previous uncertainties.
Chemistry - A European Journal, 2010
adduct isolated from Brosimum rubescens, showed potent inhibition of the binding of 5a-dihydrotes... more adduct isolated from Brosimum rubescens, showed potent inhibition of the binding of 5a-dihydrotestosterone (DHT) with the androgen receptor. Parvifolol A (2 ; Scheme 1), a natural product isolated from Gnetum parvifolium, was evaluated for the inhibitory activity in the Maillard reaction (protein glycation) associated with diabetic complications and aging of the skin. Compound 3 was synthesized and studied as an estradiol analogue. Some tricyclic 2-aryl-3,4cycloalkyl-fused benzopyrans (4, 5 ; Scheme 1) were synthesized and investigated for their high affinity to and selectivity for the estrogen receptor b over the a. Some synthetic methods have been developed for chromans by hetero-Diels–Alder (HDA) reactions. However, despite the presence of the 2-aryl group in some natural products and synthetic compounds, the synthesis of 2-aryl3,4-cycloalkyl-fused chromans has been relatively unexplored, partly due to the susceptible nature of styrenes to polymerization. To date, the reported syntheses have been largely performed for the 2-alkylcycloalkyl-fused chromans and pyranobenzopyrans. In addition, modifications on the cycloalkyl-fused rings would be difficult because the cycloalkyl or pyranyl moieties are nonfunctionalized. Moreover, different strategies were required for cyclopentyland cyclohexyl-fused compounds (4, 5). Thus, developing a general synthetic strategy for the tricyclic core of 2-aryl-3,4-cycloalkyl-fused chromans with defined stereocenters (C2, C3, and C4) and functionalizable moieties on the cycloalkyl ring would be pivotal. Recently, as part of our research in the use of solid-supported reagents in organic synthesis, our group has reported the successful generation of o-QMs and their intermolecular HDA reactions with styrene derivatives under mild conditions mediated by p-toluenesulfonic acid (p-TsOH) immobilized on silica (PTS-Si) in toluene. We now envisioned that PTS-Si could be employed to generate ortho-quinone methide (o-QM), which, upon reacting intramolecularly with the tethered dienophile (i.e. , styrenes), could form the tricyclic 2-aryl-3,4-cycloalkyl-fused chroman. As shown retrosynthetically in Scheme 2, the precursors for the intramolecular HDA reactions would be derived from aldol condensation between the benzaldehyde derivative (6) and ketone (X= H; Y=Me) or the acetophenone derivative (7) and the aldehyde (X=Me; Y=H). Synthesis of these cycloalkyl-fused chroman systems would be highly convergent and requires a similar strategy to assemble the precursors for the intramolecular o-QM/HDA reactions. [a] Dr. J. Tummatorn, Prof. Dr. S. Ruchirawat, Dr. P. Ploypradith Laboratory of Medicinal Chemistry, Chulabhorn Research Institute Vipavadee-Rangsit Highway, Bangkok 10210 (Thailand) Fax: (+662) 574-2027 E-mail : poonsakdi@cri.or.th [b] Prof. Dr. S. Ruchirawat, Dr. P. Ploypradith Program in Chemical Biology, Chulabhorn Graduate Institute Vipavadee-Rangsit Highway, Bangkok 10210 (Thailand) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200902403. Scheme 1. Examples of 2-arylcycloalkyl-fused chromans (shown with relative stereochemistry).
The Journal of Organic Chemistry, 2008
A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the intramolecular ... more A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the intramolecular cyclization of anionic benzylic ester of the aryl benzyl ether followed by oxidation employing dioxirane. With the use of microwave irradiation, licoagrodione was prepared from Claisen rearrangement of the corresponding allyl phenyl ether 1,2-diketone readily available from the Lindlar's reduction of the corresponding alkyne derivative. Subsequent removal of protecting groups then furnished the desired product.
The Journal of Organic Chemistry
The diene methyl ethers or acetates, constructed from the Li-Br exchange/addition reactions of 2-... more The diene methyl ethers or acetates, constructed from the Li-Br exchange/addition reactions of 2-vinylbenzaldehydes and 2-(but-3-en-1-yl)bromoarenes followed by etherification or acetylation of the corresponding alcohols, smoothly underwent the ring-closing metathesis (RCM) by using Hoveyda-Grubbs II as a catalyst to provide the corresponding benzannulated ( Z)-cyclononenes as single products in good yields (up to 75%). The ensuing one-pot acid-mediated transannular cyclization/nucleophilic addition at C7 furnished the corresponding tetrahydro-5 H-benzo[ c]fluorenes as single stereoisomers with the exclusive cis stereochemistry at the ring junction (C5-C6) and trans at the site of nucleophilic attack (C6-C7) on the three contiguous stereogenic centers in good to excellent yield (up to 94%). The developed strategy was general; the reaction conditions were compatible with hydride, azide, and electron-rich aromatics as nucleophiles. In addition, various methoxylated benzannulated cyclononene acetates could be employed as substrates. Thus, tetrahydro-5 H-benzo[ c]fluorenes could be prepared in four steps from appropriately substituted bromoarenes and benzaldehydes in good yields (up to 56%) with excellent stereo- and regio-control.
The Journal of Organic Chemistry
Starting from bromo/iodobenzaldehyde derivatives, the corresponding ( Z)- and ( E)-(2-stilbenyl)m... more Starting from bromo/iodobenzaldehyde derivatives, the corresponding ( Z)- and ( E)-(2-stilbenyl)methanols could be prepared in 2-5 steps via Pd-catalyzed cross-coupling reactions (Sonogashira and Heck reactions) followed by aryllithium/aryl Grignard addition. For the ( E)-stilbenes, subsequent acid-mediated cyclization using p-TsOH immobilized on silica (PTS-Si) at low temperatures furnished the 2,3- trans-1-indanols with complete stereocontrol at the C2-C3. Further oxidization of the alcohol provided the indanones, which are structurally related to the natural product paucifloral F. At higher temperatures, 1,2- and 2,3-disubstituted indenes could be selectively prepared in good to excellent yields. On the other hand, the ( Z)-stilbenes, under similar conditions (PTS-Si), did not give the indanols; only the 1,2-disubstituted indenes could be obtained. To gain further insights into the stereochemistry at C2-C3 for the ( Z)-stilbenes, hydride or azide was employed as a nucleophile; the corresponding indane products were obtained with the cis stereochemistry at the C2-C3. Thus, the ( Z)- or ( E)-olefin geometry of the substrate directed the stereoselective indanyl cyclization to furnish the cis or trans at the C2-C3 ring junction, respectively, while reaction conditions controlled the selectivity of the product types.
Tropical Journal of Pharmaceutical Research
Purpose: To modify the structure of oxyresveratrol and evaluate the obtained derivatives for effe... more Purpose: To modify the structure of oxyresveratrol and evaluate the obtained derivatives for effects on neuronal cells. Methods: Electron-withdrawing groups were selectively introduced to the aromatic ring of the core stilbene structure. Oxyresveratrol and derivatives were then evaluated for their ability to enhance the survival of P19 derived neuronal cells by XTT method, in comparison with the widely known antioxidants, Trolox and ascorbic acid. Phase-contrast microscopic images of the neurons under various conditions were also taken and analyzed. Results: Oxyresveratrol, at a very low concentration (1 ng/mL), enhanced the survival of neurons in both normal and serum-deprivation conditions. Higher activity was observed for the 5-formylated and t 5-carboxylated products. The potencies of these polyoxygenated stilbenes were far greater than those of Trolox and ascorbic acid. These observations were supported by results from the examination of the phase-contrast micrographs of the neuronal cells. Conclusion: Oxyresveratrol and some derivatives prepared in this study demonstrate significant cell protective activity and may be of therapeutic value, but further investigations in animals are required to verify their neuroprotective potentials.
![Research paper thumbnail of Divergent Strategy for the Diastereoselective Synthesis of the Tricyclic 6,7-Diaryltetrahydro-6H-benzo[c]chromene Core via Pt(IV)-Catalyzed Cycloaddition of o-Quinone Methides and Olefin Ring-Closing Metathesis](https://attachments.academia-assets.com/81679238/thumbnails/1.jpg)
](The Journal of organic chemistry, Mar 3, 2017
A divergent strategy for the synthesis of the tricyclic 6,7-diaryltetrahydro-6H-benzo[c]chromene ... more A divergent strategy for the synthesis of the tricyclic 6,7-diaryltetrahydro-6H-benzo[c]chromene core was successfully developed. The 2,3-trans, 2,4-cis trisubstituted chroman moiety was formed via highly efficient and stereoselective Pt(IV)-catalyzed cycloaddition reactions of the corresponding quinone methides with chalcones. Subsequent steps provided the common diene alcohol, which underwent BF3·Et2O-mediated Et3SiH reduction and olefin ring-closing metathesis (RCM) using Ru(II) catalysts. The sequence of the final two steps provided a handle to diversify the stereochemical outcomes at C6 as well as C10a.
Journal of natural medicines, Jan 31, 2017
Oxyresveratrol is a major active compound in the heartwood of Artocarpus lacucha. It plays an imp... more Oxyresveratrol is a major active compound in the heartwood of Artocarpus lacucha. It plays an important role in anti-tyrosinase, antioxidant, anti-inflammatory, antiviral and neuroprotective properties. There are many A. lacucha commercial products available on the market for skin whitening and anti-aging effects. To evaluate the quality of raw material from the plant, a monoclonal antibody (MAb) against oxyresveratrol was generated in this study. The immunogen was prepared by the Mannich reaction for the conjugation of oxyresveratrol and cationized bovine serum albumin (cBSA). The conjugation of oxyresveratrol-cBSA at a ratio of 1:50 was used for the immunization. The novel MAb (E4) was specific to oxyresveratrol and resveratrol. An indirect competitive enzyme-linked immunosorbent assay (ELISA) using the MAb (E4) was developed for the determination of oxyresveratrol. The linear range for the measurement of oxyresveratrol was 63-500 ng/mL and the precision (% relative standard devia...
Synlett
By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three ... more By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three steps. Subsequent Grignard/aryl lithium addition to the ketone yielded the corresponding tertiary alcohols that underwent stereoselective acid-catalyzed transannular cyclization to provide a cis-fused 5/5 bicyclic indanylindane framework exclusively. Subsequent stereoselective nucleophilic addition to the indanyl cation by hydride, water, or electron-rich aromatics furnished the 4b-aryltetrahydroindano[1,2-a]indenes in good to excellent yields (up to 92%) in the trans-C9–C9a form in up to a >99:1 diastereomeric ratio.
Chemistry - An Asian Journal, 2015
With the goaltoi mprove the aqueous solubility of lamellarins, the lactone ring in their skeleton... more With the goaltoi mprove the aqueous solubility of lamellarins, the lactone ring in their skeleton was replaced with al actam moiety in azalamellarins. However,t he reported synthetic route produced such derivatives in very low yields. Hence, this study focused on developing an efficient simplified total synthetic scheme that could furnish both azalamellarins and the parentl amellarins from the same pyrrole ester intermediates. Subsequent comparative profiling revealed that the introduced lactone-to-lactam replacement rendered these molecules less lipophilic, whereas their cancer cytotoxicity remained equipotent to that of the parentc ompounds. Interestingly,t heir inhibitory activity was significantly enhanced towards the multifaceted GSK-3b enzyme. Our results clearly demonstrate the therapeutic potential of this promising class of marine-derived natural products and justify their further development, especially into anticancer agents.
Chemistry, an Asian journal, 2015
Chemistry - An Asian Journal, 2015
Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-c... more Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-cycloalkylfused and 6-modified chromans could be prepared via ortho-quinone methides (o-QMs)/hetero-Diels-Alder (HDA) reactions of the appropriate precursors. The bromide at C6 served as a handle for introducing other substituents through palladium-catalyzed cross-coupling reactions and other functional-group transformations. Moderate to high yields (up to 80 %) and diastereoselectivities (up to > 99:1) could be obtained under [PtCl 4 ] catalysis. The preferred endo transition state during the cycloaddition reaction played an important role in governing the stereochemical outcomes at C2ÀC3ÀC4. The configurationally fixed E geometry of the bicyclic o-QMs influenced the cycloaddition reactions to favor the C2ÀC4 cis relationship.
Tetrahedron Letters, 2011
ABSTRACT A novel approach for the syntheses of lophocladines A and B has been developed. These co... more ABSTRACT A novel approach for the syntheses of lophocladines A and B has been developed. These compounds were prepared in 4-6 steps with moderate to excellent overall yields. The key step involved the nucleophilic substitution of 4-chloronicotinic acid with the carbanion generated from phenylacetonitrile. Subsequent reduction of the cyano group, lactamization and oxidation furnished lophocladine A in 50% yield over 4 steps. Further amination with various amines led to lophocladine B and its Cl analogues in good yields. In addition, the synthesized compounds were evaluated for their cytotoxicity against leukaemia cells.
Tetrahedron, 2011
Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4... more Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4þ2]cycloaddition reactions with olefins catalyzed by PtCl 4 and AuCl 3 under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl 4 was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.
Organic Letters
p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found ... more p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found to be effective in cleaving aromatic ethers containing isopropyl, tert-butyl, allyl, and benzyl groups, as well as mono-, di-, and trimethoxylated benzyl groups, in moderate to excellent yields (54−95%). These protecting groups could be selectively deprotected when they were simultaneously present on the same or different aromatic rings in a substrate. Protecting groups are important tools in organic synthesis as they have found extensive use in many different areas of complex syntheses of natural products, biomolecules, and materials. 1 Crucial features of protecting groups are their ease of preparation and removal as well as their relative stability toward different reaction conditions. A number of moieties such as benzyl, isopropyl, tert-butyl, and mono-or polymethoxylated benzyl, among others, have been developed as protecting groups for both aliphatic and aromatic hydroxy functionalities. 2 Reaction conditions for preparing and removing these protecting groups have been investigated. 3 New reagents and reaction conditions have been continually developed for protecting and/or deprotecting purposes. 4 Current awareness and interest in green chemistry has prompted many research groups, including ours, to investi
Monatshefte für Chemie - Chemical Monthly, 2010
The common structural requirements for cytotoxicity of lamellarins against two human breast cance... more The common structural requirements for cytotoxicity of lamellarins against two human breast cancer cell lines were determined using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Twenty lamellarins were selected to serve as the training set, whereas another group of six compounds were used as the test set. The best CoMFA and CoMSIA models for both cell lines yielded satisfactory predictive ability with r cv 2 values in the range of 0.659-0.728. Additionally, the contour maps obtained from both the CoMFA and CoMSIA models agreed well with the experimental results and may be used in the design of more potent cytotoxic compounds for human breast cancers. Both analyses not only suggested structural requirements of various substituents around the lamellarin skeleton for their cytotoxic activity against both human breast cancer cell lines but also revealed the molecular basis for the differences between the saturated and unsaturated D-rings of the lamellarins.
The Journal of Organic Chemistry, 2009
2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the o... more 2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene under mild conditions (0 degrees C to rt). The corresponding chromans were obtained in moderate to excellent yields (42-97%) and in moderate to excellent diastereoselectivity (up to >99:1).
ChemMedChem, 2009
Twenty-two naturally occurring and three unnatural lamellarins were synthesized and evaluated for... more Twenty-two naturally occurring and three unnatural lamellarins were synthesized and evaluated for their cytotoxicities against cancer cells. Across eleven cancer cell lines derived from six different cancer types, the IC(50) values of these compounds ranged from sub-nanomolar (0.08 nM) to micromolar (>97.0 microM). About one-fourth (6/25) and one-half (11/25) of these lamellarins are more potent than the positive control, etoposide, against at least six different cell lines and three different cell types, respectively. In general, lamellarins D, X, epsilon, M, N, and dehydrolamellarin J are significantly more potent than the other lamellarins. The IC(50) values were used to perform structure-activity relationship (SAR) studies by comparing the cytotoxic activities of several pairs of lamellarin structures that differ in selected substitution patterns. Our results not only reveal the importance of specific hydroxylation or methoxylation patterns for the first time, but also confirm prior findings and clarify some previous uncertainties.
Chemistry - A European Journal, 2010
adduct isolated from Brosimum rubescens, showed potent inhibition of the binding of 5a-dihydrotes... more adduct isolated from Brosimum rubescens, showed potent inhibition of the binding of 5a-dihydrotestosterone (DHT) with the androgen receptor. Parvifolol A (2 ; Scheme 1), a natural product isolated from Gnetum parvifolium, was evaluated for the inhibitory activity in the Maillard reaction (protein glycation) associated with diabetic complications and aging of the skin. Compound 3 was synthesized and studied as an estradiol analogue. Some tricyclic 2-aryl-3,4cycloalkyl-fused benzopyrans (4, 5 ; Scheme 1) were synthesized and investigated for their high affinity to and selectivity for the estrogen receptor b over the a. Some synthetic methods have been developed for chromans by hetero-Diels–Alder (HDA) reactions. However, despite the presence of the 2-aryl group in some natural products and synthetic compounds, the synthesis of 2-aryl3,4-cycloalkyl-fused chromans has been relatively unexplored, partly due to the susceptible nature of styrenes to polymerization. To date, the reported syntheses have been largely performed for the 2-alkylcycloalkyl-fused chromans and pyranobenzopyrans. In addition, modifications on the cycloalkyl-fused rings would be difficult because the cycloalkyl or pyranyl moieties are nonfunctionalized. Moreover, different strategies were required for cyclopentyland cyclohexyl-fused compounds (4, 5). Thus, developing a general synthetic strategy for the tricyclic core of 2-aryl-3,4-cycloalkyl-fused chromans with defined stereocenters (C2, C3, and C4) and functionalizable moieties on the cycloalkyl ring would be pivotal. Recently, as part of our research in the use of solid-supported reagents in organic synthesis, our group has reported the successful generation of o-QMs and their intermolecular HDA reactions with styrene derivatives under mild conditions mediated by p-toluenesulfonic acid (p-TsOH) immobilized on silica (PTS-Si) in toluene. We now envisioned that PTS-Si could be employed to generate ortho-quinone methide (o-QM), which, upon reacting intramolecularly with the tethered dienophile (i.e. , styrenes), could form the tricyclic 2-aryl-3,4-cycloalkyl-fused chroman. As shown retrosynthetically in Scheme 2, the precursors for the intramolecular HDA reactions would be derived from aldol condensation between the benzaldehyde derivative (6) and ketone (X= H; Y=Me) or the acetophenone derivative (7) and the aldehyde (X=Me; Y=H). Synthesis of these cycloalkyl-fused chroman systems would be highly convergent and requires a similar strategy to assemble the precursors for the intramolecular o-QM/HDA reactions. [a] Dr. J. Tummatorn, Prof. Dr. S. Ruchirawat, Dr. P. Ploypradith Laboratory of Medicinal Chemistry, Chulabhorn Research Institute Vipavadee-Rangsit Highway, Bangkok 10210 (Thailand) Fax: (+662) 574-2027 E-mail : poonsakdi@cri.or.th [b] Prof. Dr. S. Ruchirawat, Dr. P. Ploypradith Program in Chemical Biology, Chulabhorn Graduate Institute Vipavadee-Rangsit Highway, Bangkok 10210 (Thailand) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200902403. Scheme 1. Examples of 2-arylcycloalkyl-fused chromans (shown with relative stereochemistry).
The Journal of Organic Chemistry, 2008
A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the intramolecular ... more A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the intramolecular cyclization of anionic benzylic ester of the aryl benzyl ether followed by oxidation employing dioxirane. With the use of microwave irradiation, licoagrodione was prepared from Claisen rearrangement of the corresponding allyl phenyl ether 1,2-diketone readily available from the Lindlar's reduction of the corresponding alkyne derivative. Subsequent removal of protecting groups then furnished the desired product.
The Journal of Organic Chemistry
The diene methyl ethers or acetates, constructed from the Li-Br exchange/addition reactions of 2-... more The diene methyl ethers or acetates, constructed from the Li-Br exchange/addition reactions of 2-vinylbenzaldehydes and 2-(but-3-en-1-yl)bromoarenes followed by etherification or acetylation of the corresponding alcohols, smoothly underwent the ring-closing metathesis (RCM) by using Hoveyda-Grubbs II as a catalyst to provide the corresponding benzannulated ( Z)-cyclononenes as single products in good yields (up to 75%). The ensuing one-pot acid-mediated transannular cyclization/nucleophilic addition at C7 furnished the corresponding tetrahydro-5 H-benzo[ c]fluorenes as single stereoisomers with the exclusive cis stereochemistry at the ring junction (C5-C6) and trans at the site of nucleophilic attack (C6-C7) on the three contiguous stereogenic centers in good to excellent yield (up to 94%). The developed strategy was general; the reaction conditions were compatible with hydride, azide, and electron-rich aromatics as nucleophiles. In addition, various methoxylated benzannulated cyclononene acetates could be employed as substrates. Thus, tetrahydro-5 H-benzo[ c]fluorenes could be prepared in four steps from appropriately substituted bromoarenes and benzaldehydes in good yields (up to 56%) with excellent stereo- and regio-control.
The Journal of Organic Chemistry
Starting from bromo/iodobenzaldehyde derivatives, the corresponding ( Z)- and ( E)-(2-stilbenyl)m... more Starting from bromo/iodobenzaldehyde derivatives, the corresponding ( Z)- and ( E)-(2-stilbenyl)methanols could be prepared in 2-5 steps via Pd-catalyzed cross-coupling reactions (Sonogashira and Heck reactions) followed by aryllithium/aryl Grignard addition. For the ( E)-stilbenes, subsequent acid-mediated cyclization using p-TsOH immobilized on silica (PTS-Si) at low temperatures furnished the 2,3- trans-1-indanols with complete stereocontrol at the C2-C3. Further oxidization of the alcohol provided the indanones, which are structurally related to the natural product paucifloral F. At higher temperatures, 1,2- and 2,3-disubstituted indenes could be selectively prepared in good to excellent yields. On the other hand, the ( Z)-stilbenes, under similar conditions (PTS-Si), did not give the indanols; only the 1,2-disubstituted indenes could be obtained. To gain further insights into the stereochemistry at C2-C3 for the ( Z)-stilbenes, hydride or azide was employed as a nucleophile; the corresponding indane products were obtained with the cis stereochemistry at the C2-C3. Thus, the ( Z)- or ( E)-olefin geometry of the substrate directed the stereoselective indanyl cyclization to furnish the cis or trans at the C2-C3 ring junction, respectively, while reaction conditions controlled the selectivity of the product types.
Tropical Journal of Pharmaceutical Research
Purpose: To modify the structure of oxyresveratrol and evaluate the obtained derivatives for effe... more Purpose: To modify the structure of oxyresveratrol and evaluate the obtained derivatives for effects on neuronal cells. Methods: Electron-withdrawing groups were selectively introduced to the aromatic ring of the core stilbene structure. Oxyresveratrol and derivatives were then evaluated for their ability to enhance the survival of P19 derived neuronal cells by XTT method, in comparison with the widely known antioxidants, Trolox and ascorbic acid. Phase-contrast microscopic images of the neurons under various conditions were also taken and analyzed. Results: Oxyresveratrol, at a very low concentration (1 ng/mL), enhanced the survival of neurons in both normal and serum-deprivation conditions. Higher activity was observed for the 5-formylated and t 5-carboxylated products. The potencies of these polyoxygenated stilbenes were far greater than those of Trolox and ascorbic acid. These observations were supported by results from the examination of the phase-contrast micrographs of the neuronal cells. Conclusion: Oxyresveratrol and some derivatives prepared in this study demonstrate significant cell protective activity and may be of therapeutic value, but further investigations in animals are required to verify their neuroprotective potentials.
The Journal of organic chemistry, Mar 3, 2017
A divergent strategy for the synthesis of the tricyclic 6,7-diaryltetrahydro-6H-benzo[c]chromene ... more A divergent strategy for the synthesis of the tricyclic 6,7-diaryltetrahydro-6H-benzo[c]chromene core was successfully developed. The 2,3-trans, 2,4-cis trisubstituted chroman moiety was formed via highly efficient and stereoselective Pt(IV)-catalyzed cycloaddition reactions of the corresponding quinone methides with chalcones. Subsequent steps provided the common diene alcohol, which underwent BF3·Et2O-mediated Et3SiH reduction and olefin ring-closing metathesis (RCM) using Ru(II) catalysts. The sequence of the final two steps provided a handle to diversify the stereochemical outcomes at C6 as well as C10a.
Journal of natural medicines, Jan 31, 2017
Oxyresveratrol is a major active compound in the heartwood of Artocarpus lacucha. It plays an imp... more Oxyresveratrol is a major active compound in the heartwood of Artocarpus lacucha. It plays an important role in anti-tyrosinase, antioxidant, anti-inflammatory, antiviral and neuroprotective properties. There are many A. lacucha commercial products available on the market for skin whitening and anti-aging effects. To evaluate the quality of raw material from the plant, a monoclonal antibody (MAb) against oxyresveratrol was generated in this study. The immunogen was prepared by the Mannich reaction for the conjugation of oxyresveratrol and cationized bovine serum albumin (cBSA). The conjugation of oxyresveratrol-cBSA at a ratio of 1:50 was used for the immunization. The novel MAb (E4) was specific to oxyresveratrol and resveratrol. An indirect competitive enzyme-linked immunosorbent assay (ELISA) using the MAb (E4) was developed for the determination of oxyresveratrol. The linear range for the measurement of oxyresveratrol was 63-500 ng/mL and the precision (% relative standard devia...