Valiolamine analog

Opening a new route to valiolamine analogs, this work broadens the scope of the enzymatic aldol reaction combining in one pot the formation of two carbon-carbon bonds with high stereoselectivity. We demonstrate a short efficient synthesis of new nitro- and aminocychtols that considerably reduces the laborious... 

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

Scheme 4.13 Multi-enzyme route for the synthesis of aminocyclitol analogs of valiolamine...

The aminocyclitol synthesis mediated by DHAP-dependent aldolases consists of a double aldol reaction, the first one enzymatically controlled by aldolases and the second one a spontaneous intramolecular nitro-aldol reaction (i.e., the Henry reaction) (Scheme 10.18). The latter makes use of the electrophilic carbonyl unit introduced by the first aldol addition on the nucleophilic character of carbon bonded to a nitro group installed from the acceptor (e.g., 62). This twofold C—C bond-forming reaction cascade was shown to deliver, after nitro group reduction, aminocyclitol analogs of valiolamine (63), of interest as inhibitors of intestinal glycosidases [141]. 

The mild conditions of the olefin metathesis reaction make it an ideal method for the preparation of cyditols and carbasugars [51, 52]. In general, the syntheses start from readily available carbohydrate derivatives that are converted to dienes and then submitted to RCM conditions. The resulting functionalized cyclohexenes are then converted to the target molecules in a few straightforward steps [53b]. According to this principle, the syntheses of (+)-cyclophellitol (230) (Scheme 1.40) [54], valienamine (233) (Scheme 1.41) [53, 55], valiolamine (236) (Scheme 1.42) [56], conduritol derivatives 238-240 (Scheme 1.43) [57], phosphatidyl inositol [58], and analogs (243) (Scheme 1.44) [59] have been reported. 

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