Trehalase synthesis

The chemical synthesis of derivatives and emalogs has long coimnanded much interest, as such compounds are required for the study of structure—activity relationships in the action of trehalases (23,28), may serve as substitutes for 51 in the synthesis of cord-factor analogs to be used as probes in the field of mycobacterial biochemistry (29, 30), and could possibly prove to possess interesting properties as enzyme inhibitors or antibiotic agents. 

In the early days of this Advances series, authors were offered the opportunity to record experimental procedures as part of their contributions, but this has been rarely used in recent years. However, the practice is revived here in the article by El Nemr and El Ashry (Alexandria) on the synthesis of trehazolin, a natural nitrogen-containing pseudodisaccharide that is an inhibitor of the enzyme trehalase, together with various analogues. These synthetic targets can be approached in a wide variety of ways, and the authors present for each synthetic sequence sufficient detail to permit an experienced synthetic chemist to repeat the procedure. 

S. Ogawa, C. Uchida, and Y. Yuming, Synthesis of aminocyclitol moieties of trehalase inhibitors, trehalostatin and trehazolin, J. Chem. Soc. Chem. Commun. (1992) 886-888. 

C. Uchida, T. Yamagishi, and S. Ogawa, Total synthesis of the trehalase inhibitors trehalostatin and trehazolin, and of their diastereoisomers. Final structural confirmation of the inhibitor, J. Chem. Soc. Perkin Trans., 1 (1994) 589-602. 

S. Ogawa and C. Uchida, Total synthesis of trehalase inhibitor, trehazolin, Chem. Lett. (1993) 173-176. 

In Section IX,2, some mention was made of the role of a,a-trehalose as a storage carbohydrate in yeasts. Studies on its metabolic control have shown that extracts of bakers yeast can be separated into two protein fractions, (i) neither of which can split a,a-trehalose, (it) but, recombined and incubated with Mg2 , ATP, and adenosine 3, 5 -monophosphate (cAMP), they form active a,a-trehalase.682 Work on the other major carbohydrate-reserve in yeasts, namely, glycogen,683 was reviewed in Ref. 513 later work has been described on the regulation of glycogen synthesis by Saccharomyces cerevi-stoe884,685 and Candida tropicalis.686... 

Trehazolamine. Chiara has described a synthesis of trehazolamine, the aglycon of trehazolin, a powerful inhibitor of trehalase, wherein a pinacol cyclization provided the necessary cyclopentane framework (Eq. 3.2) [17]. Thus, treatment of the tetrabenzyl-protected keto aldehyde, derived from D-glucose, with Sml2 furnished the two cis diols exclusively as a 1 1 mixture of isomers in excellent yield (>90%) [18]. Previous studies of five-membered ring formation mediated by SmE have also reported good cis/trans selectivity, presumably due to the intervention of a samarium chelate. 

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