Synthesis of a Glyoxalase I Inhibitor from Streptomyces griseosporeus NIIDAet OGASAWARA

✍ Scribed by Sohail Mirza; Louis-Pierre Molleyres; Andrea Vasella

• Book ID: 102856838
• Publisher: John Wiley and Sons
• Year: 1985
• Tongue: German
• Weight: 638 KB
• Volume: 68
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19850680425

✦ Synopsis

Abstract

The pseudolactones 6 and 12 were prepared in a straightforward way from methyl α‐D‐glucopyranoside and methyl α‐D‐mannopyranoside, respectively. The pseudolactone 6 reacted with tert‐butyl lithioacetate to give the protected, trihydroxylated cyclohexenone carboxylate 7 (51 %). The sterically hindered, L‐ribo‐configurated pseudolactone 12 reacted with diethyl ethylphosphonate and dimethyl methylphosphonate to give the protected trihydroxycyclohexenones 17 (49 %) and 18 (62 %), respectively. The hydroxymethylated cyclohexenone 21 was obtained from 18 by treatment with Me~2~AlSPh and then formaldehyde, oxidation of the product 19, and elimination. Deprotection of 21 gave 2, identical with KD16‐Ul. Esterification of 2 gave 1, identical with the title compound. Alternatively, 1 was obtained in higher yields by esterification of 21, followed by deprotection of the hydroxy groups. This synthesis gave 1 and 2 from methyl α‐D‐mannopyranoside in an overall yield of 18 and 20 %, respectively, confirming their absolute configuration.