Stereoselective Synthesis of Differentially Protected Derivatives of the Higher Amino Sugars Destomic Acid and Lincosamine from Serine and Threonine.
The aminoheptose 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-BOC threoninal. The parallel sequences feature BF(3)-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 intermediates led to the gamma-lactols 3.2 and 5.8, respectively. In the former 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 silyl ether cleavage, acidic hydrolysis, and bis-acetonide formation. Inversion of the C7 hydroxyl grouping was effected by the Mitsunobu methodology with p-NO(2)C(6)H(4)CO(2)H. Subsequent hydrolysis, cleavage of the BOC grouping, and N-acetylation afforded the lincosamine derivative 6.7.
Marshall
James A.
JA
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22903.
Beaudoin
Serge
S