N. André Sasaki

A novel approach to the synthesis of optically pure non protein α-amino acids in both L and D configurations from L-serine

Abstract Efficient syntheses of (2R)-2-Boc-amino-3-phenylsulfonyl-l-propanol 3 and its enantiomer 9 from L-serine are described. The potential of these compounds in a novel general method for the synthesis of optically pure non protein α-amino acids in both the L and D configurations is exemplified by the preparation of N-Boc-L-and D-homophenylalanine, -norvaline and -norleucine.

Enantioselective synthesis of cyclopropane α-amino acids: Synthesis of N-Boc-cis-(2S,3R,4S)-3,4-methanoproline and N-Boc-(2S,3R,4S)-3,4-methanoglutamic acid

Abstract The title compounds were synthesized by a 5-step facile transformation of the key intermediate 4, itself obtained by a “one-pot” sulfone-mediated cyclopropanation from chiral synthon (R)-1 and (2 R )-glycidyl triflate.

A versatile method for the synthesis of (S)- or (R)-cycloalkylglycines, (S)- or (R)-N-Heterocyclic and α,β-unsaturated N-heterocyclic α-amino acids

Abstract Two different types of cyclic α-amino acids, cycloalkylglycines and N-heterocyclic α-amino acids, were prepared in optically pure form from the same chiral synthon 1- ( R ) (or 1- ( S )) simply by altering the quantity or type of base required for anion formation. Elaboration of the heterocyclic intermediate 3 provided α,β-unsaturated N-heterocyclic α-amino acids.

An efficient method for the stereoselective synthesis of cis-3-substituted prolines: conformationally constrained α-amino acids

Abstract An efficient synthesis of enantiomerically pure cis-3-substituted prolines is reported. Key steps involve the stereoselective organocuprate addition to the (E)-α,β-unsaturated ester 1 , obtained from the Garners aldehyde, and expedient oxidation–cyclization sequences.

Stereoselective synthesis of optically pure β,γ-unsaturated α-amino acids in both L and D configurations

A new method for the stereoselective synthesis of optically pure β,γ-unsaturated α-amino acids in L or D configuration is developed by reacting the dilithiate of (2R)-2-Bocamino-3-phenylsulfonyl-1-(2-tetrahydropyranyloxy)propane 1 or its (2S)-antipode 2, both derived from L-serine, with aldehyde, followed by stereoselective olefin formation, desulfonylation and oxidation.

A Practical Synthesis of (2S,3R,4S)-4-Hydroxyisoleucine, A Potent Insulinotropic α-Amino Acid from Fenugreek

An efficient eight-step synthesis of optically pure (2S,3R,4S)-4-hydroxyisoleucine (1), a potent insulinotropic α-amino acid found in the seeds of fenugreek (Trigonella foenum-graecum L.), is achieved in 39% overall yield. The method is suitable for large-scale production of the title compound. The key steps involve the biotransformation of ethyl 2-methylacetoacetate to ethyl (2S,3S)-2-methyl-3-hydroxybutanoate (2) with Geotrichum candidum and an asymmetric Strecker synthesis. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Enantioselective synthesis of (2S,3S)- and (2R,3R)-pyrrolidine-2,3-dicarboxylic acids : conformationally constrained (S)- and (R)-aspartic acid analogues

Abstract The title compounds were prepared from the key intermediate 2 and its enantiomer at C2, derived from chiral synthons 1 - ( R ) and 1 - ( S ), respectively, by ethoxycarbonylation, desulfonylation and conversion to carboxylic acid.

N-Terminal 2,3-diaminopropionic acid (Dap) peptides as efficient methylglyoxal scavengers to inhibit advanced glycation endproduct (AGE) formation

2,3-Diaminopropionic acid (Dap) and N-terminal Dap peptides have been found to inhibit in vitro protein-modifications by methylglyoxal (MG), one of the highly reactive alpha-dicarbonyl compounds. MG scavenging potency of the newly synthesized N-terminal Dap peptides is demonstrated by RP-HPLC, SDS-PAGE and non-denaturing PAGE analysis, assays for enzymatic activity and cell viability study and was compared with that of known AGE inhibitors, such as aminoguanidine, pyridoxamine, metformin and carnosine. Two addition products of MG and L-Dap-L-Leu are separated by HPLC and their chemical structures are characterized by (1)H and (13)C NMR spectroscopy to indicate that both of them are pyrazines derived from 2 molecules of MG and 1 molecule of L-Dap-L-Leu. Mutagenic activities of L-Dap-L-Leu and L-Dap-L-Val and their metabolites according to the Ames assay are found to be negative.

A novel method for chirospecific synthesis of 2,5-disubstituted pyrrolidines

Abstract One-pot ring formation using (R) - 1 or (S) - 1 as a nucleophile and homochiral glycidyl triflate (R) - 2 or (S) - 2 as an electrophile a pivotal intermediate 4 which can be transformed into a 2,5-disubstituted pyrrolidine with any desired stereochemistry at the C-2 and C-5 positions.

A novel approach for the asymmetric synthesis of (3S,4R)-3-amino-4-alkyl-2-piperidinones: conformationally constrained dipeptides

Abstract A straightforward method is developed for the synthesis of enantiopure (3S,4R)-3-amino-4-alkyl-2-piperidinone derivatives, six-membered lactam-bridged dipeptides, via highly diastereofacial selective 1,4-addition of organocuprate to the chiral oxazolidine α,β-unsaturated ester 1 as the key step.