Synthesis of a Glyoxalase I Inhibitor from Streptomyces griseosporeus NIIDAet OGASAWARA

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 Me2AlSPh 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.

Recent Advances in the Conversion of Carbohydrate Furanosides and Pyranosides into Carbocycles

“…Historically, a tandem fragmentation/Henry-type cyclization reaction provided the first examples in which cyclohexane [21] and cyclopentane derivatives [22] were obtained from a carbohydrate. An elegant application of the Fujimoto ± Belleau reaction by Vasella et al [23] and the anionic rearrangement of anhydrosugars [24] are also examples of this strategy. Some of the above transformations allow the direct conversion of carbohydrate furanosides and pyranosides into carbocyclic polyols.…”

Total Syntheses of Useful Bioactive Compounds

“…The first synthesis was achieved by Vasella et al in which methyl a-d-glucopyranoside was effectively used as starting material. [14] As mentioned in the synthesis of the PF1092s (34±36), [11] the SnCl 4 -promoted, aldol-like cyclization of phenylsulfonyl enol silyl ethers containing a dimethyl acetal has been explored extensively in our laboratories. This transformation is ideally suited to the synthesis of carbocycle-containing natural products and carbasugars, since the core skeleton arises after appropriate replacement of the phenylsulfonyl group.…”

“…(+)-4-Acetoxy-3-hydroxyethyl-2-azetidinone, that is (3R,4R)-4-acetoxy-3-[(R)-1'-hydroxyethyl]-2-azetidinone (14), and its derivatives are well-known as the highly versatile intermediates [5] for the synthesis of carbapenem antibiotics such as thienamycin (15), imipenem, meropenem and so on (Scheme 1).…”

“…Oxidative decarboxylation of 13 by Pb(OAc) 4 gave exclusively the desired (+)-4-acetoxy-3-hydroxyethyl-2-azetidinone (14) with removal of silyl groups. [7] This was identical in all respects with the authentic sample, which was prepared from the commercially available O-tert-butyldimethylsilyl derivative.…”

Neue Fortschritte bei der Umwandlung von Kohlenhydratfuranosiden und -pyranosiden zu Carbocyclen

“…Geschichtlich gesehen ist die Tandemreaktion aus Fragmentierung und Cyclisierung vom Henry-Typ das erste Beispiel, in dem Cyclohexan- [21] und Cyclopentanderivate [22] aus einem Kohlenhydrat erhalten wurden. Auch die elegante Anwendung der Fujimoto-Belleau-Reaktion durch Vasella [23] und die anionische Umlagerung von Anhydrozuckern [24] sind Beispiele für diese Strategie. Einige der oben beschriebenen Reaktionen ermöglichen eine direkte Umwandlung von Kohlenhydratfuranosiden und -pyranosiden zu carbocyclischen Polyolen.…”