STEREOSELECTIVE SYNTHESIS OF DIFFERENTIALLY PROTECTED DERIVATIVES OF THE HIGHER AMINO-SUGARS DESTOMIC ACID AND LINCOSAMINE FROM SERINE AND THREONINE

The aminoheptpse destomic acid (3.5) and the aminooctose lincosamine ( 6.8) were synthesized in protected form by parallel sequences starting from the oxazolidine derivatives 2.4 and 5.1 of N-CBz serinal and N-B OC threoninal. The parallel sequences feature BF3-promoted addition of the (R)-gamma-OTBS allylic stannane 2.8 to the homologated enals 2.7 and 5.4, respectively, followed by stereoselective bis-dihydroxylation of the derived bis-OTBS ethers 2.10 and 5.6. Regioselective oxidative cleavage of the less hindered vicinal diol moieties of these intermed iates led to the gamma-lactols 3.2 and 5.8, respectively. In the forme r case, treatment with TBAF and subsequent hydrolysis removed the OTBS and acetonide protecting groups affording the destomic acid precursor , pyranose 3.4. Lactol 5.8 was converted to the pyranoside 6.3 by sily l ether cleavage, acidic hydrolysis, and bis-acetonide formation. Inve rsion of the C7 hydroxyl grouping was effected by the Mitsunobu method ology with p-NO2C6H4CO2H. Subsequent hydrolysis, cleavage of the BOC g rouping, and N-acetylation afforded the lincosamine derivative 6.7.