High-Yielding Diastereoselective syn-Dihydroxylation of Protected HBO: An Access to D-(+)-Ribono-1,4-lactone and 5-O-Protected Analogues

A diastereoselective chemoenzymatic synthetic pathway to D-(+)-ribono-1,4-lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose-based levoglucosenone (LGO). This route involves a sustainable Baeyer-Villiger oxidation of LGO to produce enantiopure (S)-gamma-hydroxymethyl-alpha,beta-butenolide (HBO) that is further functionalized with various protecting groups to provide 5-O-protected gamma-hydroxymethyl-alpha,beta-butenolides. The latter then undergo a diastereoselective and high-yielding syn-dihydroxylation of the alpha,beta-unsaturated lactone moiety followed by a deprotection step to give D-(+)-ribono-1,4-lactone. Through this 4-step synthetic route from LGO, D-(+)-ribono-1,4-lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5-O-tert-butyldimethylsilyl-, 5-O-tert-butyldiphenylsilyl- as well as 5-O-benzyl-ribono-1,4-lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.