Synthesis of α-alkyl and α-functionalized methyl-α-amino acids

✍ Scribed by P. Bey; J.P. Vevert

• Publisher: Elsevier Science
• Year: 1977
• Tongue: French
• Weight: 186 KB
• Volume: 18
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)93073-4

✦ Synopsis

As part of our program aimed at the design of specific enzyme inhibitors, we have been interested in the synthesis of a-alkyl substituted-u-amino acids of type 1 (Y -H or heteroatom functions). R CH3 The classical route to a-alkyl substituted-a-amino acids consists of a Bucherer or a Strecker reaction on the corresponding ketones'. These methods which imply hydrolyses of hydantoin or a-amino nitrile intermediates to the corresponding a-amino acids, suffer from requiring drastic conditions that are not always compatible with sensitive functionalities 2 . More recently, new procedures based on alkylation of anions of type 2 derived from various protected forms of a-amino acids have been developed. The protecting groups on the carboxyl and on the amine functions serve at the same time the purpose of activating the a position. Anions from a-isocyano 3 carboxylate (R,=OEt, R2, R3=1C) , azlactone (R,, R2, R,=zp 5 _Q4' o-nitro carboxylate (RI=OEt, R2=R3=0) , a-[Bis(alkylthio)methylenamino] carboxylate (R)=OEt, R2, R3=ZC(-SR), and a-benzylidene amino lactam (R,=N<; R2, R3= =CB!ii)7 have been used successfully. In line with this approach, we have investigated the use of Schiff base ester 3 of a-amino acids as a general synthon for the synthesis of a-alkyl and a-functionafised methyl-a-amino acids. A recent report by Stork8 describing a similar synthon prompts us to disclose our results.