Straightforward entry to the pipecolic acid nucleus. Enantioselective synthesis of baikiain (original) (raw)
Related papers
A new method for the enantioselective synthesis of N-Boc-a,a-disubstituted a-amino acids
Tetrahedron, 2001
Boc-a,a-disubstituted a-amino acids has been developed. The starting materials are diastereomerically pure 3,3-disubstituted allyl alcohols, prepared by DIBAL-H reduction of the corresponding unsaturated esters derived from carbocupration of an acetylenic ester or from Wadsworth±Emmons ole®nation of a ketone. Sharpless epoxidation of the allylic alcohols provided enantiomerically enriched epoxy alcohols that were submitted to nucleophilic ring-opening under Crotti's conditions (N 3 Na/LiClO 4) to give 3-azido-1,2-diols. Hydrogenation and in situ protection provided the N-Boc-3-amino-1,2-diols that were oxidatively cleaved to the a,a-disubstituted N-Boc-a-amino acids. Protected a-methyl-a-phenylglycine and a-methylisoleucine have been prepared by this methodology.
A Highly Diastereoselective Synthesis of New Polyhydroxy 2-Aminonorbornanecarboxylic Acids
The Journal of Organic Chemistry, 2001
Our recent research is directed toward the synthesis of -heterosubstituted carbocyclic amino acids [1][2][3][4] in which the skeleton of natural amino acid is included. For this reason and for their rigidity, they appear to be interesting compounds as biological targets. In particular, the 2-aminonorbornanecarboxylic acid derivatives, because of the bulkiness and apolarity of the ring and the metabolic stability, are characterized by different biological activities. As evidenced by recent literature, a new and very promising research field is related to the preparation of hydroxy-and polyhydroxycarbocyclic amino acids, which are considered mimetic of carbohydrates but are characterized by a greater metabolic stability. 4,6 In continuing our research in this area, we now report on the highly diastereoselective synthesis of 2-amino-3,6-dihydroxynorbornanecarboxylic acid 14 and of 2-amino-3,5,6-trihydroxynorbornanecarboxylic acids 15-18. Our purpose in the synthesis of the polyhydroxylated norbornanecarboxylic acid derivatives is related to the possibility to change the polarity of this nucleus and their biological properties. As known, in many cases, polar substituents are responsible for the interactions between the substrate and the enzymatic receptor and their spatial arrangement is determinant to realize those interactions. So, the preparation of compounds 14-18 having several hydroxy groups in a specific position and in a controlled spatial arrangement represents an important goal. The key starting materials for the preparation of these compounds are the exo-and endo-2-amino-3-hydroxynorbornenecarboxylic acid derivatives 3 and 4, including the serine skeleton, which were synthesized recently in our laboratory. 3 The cycloaddition reaction between oxazolone (Z)-1 and cyclopentadiene (2) was carried out using litium perchlorate as the catalyst, giving a mixture of cycloadducts exo-3 and endo-4. After the addition of anhydrous ethanol to the crude reaction mixture, cycloadducts 3 and 4 were transformed into the corresponding esters exo-5 and endo-6 (70:30 ratio), which were isolated in a 70% overall yield (Scheme 1). Esters 5 and 6 were the key starting materials for the preparation of the 5,6-dihydroxy derivatives in which the cis or trans relationship between the two hydroxy groups exists (Scheme 1). Treatment of ester exo-5 with a catalytic amount of osmium tetraoxide in the presence of an excess of N-methylmorpholine N-oxide in a mixture of acetone/water allowed the formation of the cis-dihydroxy derivative exo-7, as a single diastereoisomer, in 74% yield. The derivative endo-8 was isolated in 80% yield when starting from endo-6 and operating under the same conditions.
A new method for the enantioselective synthesis of N-Boc-α,α-disubstituted α-amino acids
Tetrahedron, 2001
A new method for the enantioselective synthesis of N-Boc-α,α-disubstituted α-amino acids has been developed. The starting materials are diastereomerically pure 3,3-disubstituted allyl alcohols, prepared by DIBAL-H reduction of the corresponding unsaturated esters derived from carbocupration of an acetylenic ester or from Wadsworth–Emmons olefination of a ketone. Sharpless epoxidation of the allylic alcohols provided enantiomerically enriched epoxy alcohols that were submitted to nucleophilic ring-opening under Crotti's conditions (N3Na/LiClO4) to give 3-azido-1,2-diols. Hydrogenation and in situ protection provided the N-Boc-3-amino-1,2-diols that were oxidatively cleaved to the α,α-disubstituted N-Boc-α-amino acids. Protected α-methyl-α-phenylglycine and α-methylisoleucine have been prepared by this methodology.Graphic
Tetrahedron: Asymmetry, 1999
A versatile, non-alkylative enantioselective synthesis of unsaturated α-amino acids based on the Sharpless asymmetric epoxidation has been developed. Enantiomerically enriched trans epoxy alcohols bearing unsaturated substituents were prepared and submitted to regio-and stereospecific ring-opening with p-methoxybenzylamine as a nucleophile, leading to anti-3-(p-methoxybenzylamino)-1,2-diols which were further protected by reaction with Boc 2 O. The 1,2-diol fragment was then oxidatively cleaved by a sequential treatment with sodium periodate and sodium chlorite to afford the corresponding amino acid. Using this methodology, doubly N-protected (pmethoxybenzyl and Boc) allyl glycine, 3-butenyl glycine and 4-pentenyl glycine have been prepared in three synthetic steps from the corresponding allyl alcohols. As a demonstration of the orthogonal nature of the nitrogen protection, both protecting groups have been selectively removed from the fully protected amino ester.
Synthesis of Heterocyclic g-Amino-a,b-unsaturated Acid Derivatives and Peptide-Heterocycle Hybrids
Heterocycles, 2003
The syntheses of the γ-amino-α,β-unsaturated esters [(R)-4, (S)-5, and (±)-6] are reported. The methodology for the preparation of these triannular heterocycles involves two synthetic sequences from N-substituted amino alcohols: a 'one-pot' sequential Swern oxidation-Wittig reaction and an intramolecular Heck reaction. The γ-amino-α,β-unsaturated ester [(R)-4] has been used for the synthesis of the peptideheterocycle hybrids (19)(20)(21).