A general synthesis of α-vinyl-α-amino acids

✍ Scribed by W.J. Greenlee; D. Taub; A.A. Patchett

• Publisher: Elsevier Science
• Year: 1978
• Tongue: French
• Weight: 184 KB
• Volume: 19
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)95122-6

✦ Synopsis

In connection with our experiments directed toward the design of specific enzyme inhibitors,l we desired an efficient route to vinyl amino acids of type 1.

3 Although these might be obtained by partial reduction of the corresponding ethynyl amino acids as has been shown for a-vinyl DOPA (R = 3,4-dihydroxyphenylmethyl), 192 we sought a more direct method for their preparation. We now wish to report the use of dehydroamino acid derivative 2 as a synthon for a-vinyl amino acids. The recently reported route to a-amino acids by alkylation of the anion derived from benaalglycinate z5 coupled with the well-known deconjugative alkylation of enolates derived from a,B-unsaturated carbonyl systems, suggested that the anion formed upon deprotonation of 2 would undergo alkylation at the a-position. R CH2=CH-&OH Schiff base 213 was conveniently prepared from (DL)-8-chloro-a-aminobutyric acid methyl ester hydrochloride @).14 CH3CH-CH-C02CH3 II Cl NH2.HCl CH3\C=C/C02CH3 H' 'N=CHPh 90% Ph-CHO * Et3N, MgS04 CH2C12 20" C, 24 hrs 1) LiN[Si(CH3)212 2) H20 Cl N=CHPh I DBU CH2C12 20" c, CH3CH=T-C02CH3 N=CHPh 2 -1 hr 80% 60:40 E:Z Attempts to prepare a-vinylglycine (1, R=H)4a'b by quenching anion 4 with water or acetic acid at either -JO°C or at room temperature led instead to isolation of the pure E isomer of 2. Unlike the anion derived from benzalglycinate 2,5 anion 5 does not undergo Michael addition to methyl acrylate or acrylonitrile at -70°C. Reaction of fL with other electrophiles is now being studied.