Studies concerning lysergic and dihydrolysergic acid α-hydroxyethylamides (original) (raw)
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The Journal of Organic Chemistry, 1988
A practical approach to selectively protected chiral threitols and erythritols is described. These functionalized synthons are easily prepared from the title acids. Recently, we reported the synthesis of 1,2-O-protected L-threitols from L-ascorbic acid.2 While these and their D-isomers are easily obtained from D-and L-tartaric acids, the same is not true for the chiral erythritols, which are derivable from meso-tartaric acid. In this paper we now dascribe the hitherto unknown, 1,2(R)-O-isopropylideneand 1,2(R)-O-benzylideneerythritols from D-isoascorbic acid.3 These versatile intermediates were used to prepare other suitably protected triols and tetrols, synthons with unlimited synthetic utility (Scheme I). T h e present approach circumvents inherent disadvantages encountered in the preparation of related isomeric compound^.^ T h e pathways are shorter, the choice of chirality is feasible, and it allows the preferential protection of one hydroxy group a t a time, whether primary or ~e c o n d a r y ,~ an option not easily afforded by the aforementioned methods4 or the nacleophilic opening of chiral epoxides.6 0 % I Bn = CHZPh zylate8 afforded (2R,3S)-l,3,4-triO -benzylbutane-1,2,3,4tetrol (7)9 in good yield. Regiospecific reductive cleavage of a benzylidene rinebJo offered another route to 7. This pathway used the pro
A new procedure has been developed for synthesizing enantiomerically pure p-amino acids, a-hydroxy-P-amino acids and certain alkaloids from aspartic acid. By protection, anhydride formation and regioselective reduction, L-aspartic 10 is converted to the N-tosylamino lactone 12. Hydroxylatioii of 12 by an oxaziiidine gives the tr.u/is-2-Iiydroxy-3-N-tosylaiiiiiio derivative 20. Opening of 12 and 20 by triinethylsilyl iodide and ethanol affords the iodo-homoserine esters 13 and 21 respectively. Subinission of 13 and 21 to Gilmaii reagents followed by saponification and deprotection gives 4-substituted 3-amino and 3-ainino-2-hydroxybutyric acids . exemplified by the syntheses of cyclohexylnorstatine (25), and the coinponents of bestatin (23, R=Ph) and inicroginin (14). Certain p-amino acids are transformed into soleilopsin A (33) and indolizidine 209D (41).
Drug testing and analysis, 2016
Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N(6) -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the 'research chemicals'/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-H...
Synthetic studies in dihydroindole and indole alkaloids
1973
A synthetic approach toward the synthesis of vindoline (3) and a reinvestigation of the total synthesis of vincaminoridine (4) and epivincaminoridine (4a) is described. The synthetic sequence involves alkylation with benzyl chloride of the monosodium salt of propane-l,3-diol to give y-benzyloxypropanol (197). Treatment of 197 with thionyl chloride afforded benzyl-ychloropropyl ether (198). Alkylation of ethyl diethyl malonate with 198 provided diethyl Y~D enz yl ox yP ro Pyl etn yl malonate (134). Basic hydrolysis of 134 gave y-benzyloxypropylethyl malonic acid (199), which upon decarboxylation provided 2-(y-benzyloxypropyl)-butanoic acid (200). The monoacid (200) was esterified with ethanol to provide ethyl tx-(y-benzyloxypropyl)-butanoate (135). Alkylation of 135 with allyl bromide gave ethyl-a-(y-benzyloxypropyl)-a-allylbutanoate (201), which upon treatment with osmium tetroxide and sodium periodate gave ethyl a(y-benzyloxypropyl)-a-(a-formylmethyl)butanoate (140). Condensation of 140 with 6-methoxy tryptamine afforded the tetracyclic lactam (150). Lithium aluminum hydride reduction of the latter, followed by hydrogenolysis of the benzyl group gave two isomeric tetracyclic alcohols (204). These intermediates were converted via their mesylate derivatives to the quaternary salts (205), which upon treatment with potassium cyanide gave the isomeric cyanides (216). Acid hydrolysis of 216 gave the corresponding carbomethoxy derivative (151). Alkylation of 151 i i iwith methyl iodide provided dl-vincaminoridine (4) and dlepivincaminoridine (4a). Transannular cyclization of the latter substances gave the pentacyclic aspidosperma-type system (195). The degradation sequence involved acid hydrolysis of vindoline (3) to provide desacetyl vindoline (224), which upon catalytic hydrogenation gave desacetyldihydrovindoline (225). Pyrolysis of 225 afforded the ketone (86), which upon treatment with dimethyl carbonate provided the g-ketoester (226). Treatment of the sodium enolate of 226 with oxygen-hydrogen peroxide gave the hydroxy ketoester (227). Treatment of desacetyldihydrovindoline (225) with N,Nthiocarbonyldiimidazole gave the thiocarbonate derivative (230), which upon desulfurization with Raney nickel afforded the unsaturated ester (231). Catalytic hydrogenation of 231 gave the saturated ester (232) , which upon treatment with lithium diisopropyl amide and oxygen-hydrogen peroxide provided the hydroxyester (234). The saturated ester 232 was converted to the alcohol derivative (237) by reduction with aluminum hydride. Oppenauer oxidation of 237 gave the aldehyde (238). Finally potassium permanganate oxidation of the unsaturated ester (231) gave 5-membered lactam (240), 6-membered lactam (241), N-formyl-5-membered lactam (242), ct and N Q-formyl-6-membered lactam (243) .
Russian Journal of Organic Chemistry, 2010
Acylation of N-substituted exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0 3,7 ]nonane-endo-9-carboxamides on heating in boiling glacial acetic acid gave the corresponding trans-diacetoxy imides of the norbornane series. The effect of the reaction time on the product composition was studied in the reaction with exo-2-hydroxy-N-(4-methylphenyl)-5-oxo-4-oxatricyclo[4.2.1.0 3,7 ]nonane-endo-9-carboxamide. The structure of the resulting norbornane-2,3-dicarboximides was confirmed by IR, 1 H NMR, and mass spectra, and the structure of N-(2,5-dimethylphenyl)-exo-2,endo-3-diacetoxybicyclo[2.2.1]heptan-endo-5,endo-6-dicarboximide was additionally proved by X-ray analysis.
Synthesis of Novel Non-Isoprenoid Phenolic Acids and 3-Alkylpyridines
Pure and applied …, 2005
A new strategy has been developed for the synthesis of naturally occurring 6-alkenyl phenolic acids and 3-alkylpyridine alkaloids of biological importance. This strategy makes use of the proper substituted aryl or pyridyl sulfone as the potent intermediate. A carbanion was generated from the sulfone by treating it with NaH in dimethylformamide (DMF) at-5°C and was used for alkylation reaction with alkyl/alkenyl bromide in DMF at 0°C to give product, which, on reduction with sodium-amalgam, yielded the desired natural product. Using this methodology, we have synthesized 11 natural 6-alkyl/alkenyl salicylic acids, which were known to possess strong antimicrobial activities against many pathogens and had also shown molluscicidal activity against the snail Biomphalaria glabrata. This methodology was also extended to synthesize two natural 3-alkylpyridine alkaloids that were known to possess strong cytotoxic activity against P-388 murine leukemia cells with IC 50 values of 1-2.3 µg/ml. Taking leads from these natural products, we have also synthesized a number of related compounds in order to find a potential drug candidate for the future. This paper presents the highlights of the work done on the synthesis of these two classes of compounds. *Paper based on a presentation at the 24 th International Symposium on the Chemistry of Natural Products and the 4 th International Congress on Biodiversity, held jointly in Delhi, India, 26-31 January 2004. Other presentations are published in this issue, pp. 1-344. ‡ Corresponding author S. C. JAIN et al.