The key aglycone, oleandolide, has been synthesized by coupling two segments of Cl-C7 and C&C14 portions, which are enantiospecifically derived from methyl U-L-and Drhamnosides, respectively. Oleandomycin (1) is a medicinally important 14-membered-ring macrolide antibiotic. Herein we describe the first total synthesis of oleandomycin (l), which has been already derived from the key aglycone, oleandolide (21), by introduction of the two sugar moieties in our laboratories.1) The construction of the aglycone 21 is based on coupling of the Cl-C7 segment 9 and the C8-C&) segment 14. In reaching both segments 9 and 14, we took advantage of our recently developed epoxide swinging reaction3) of methyl CC-L-and D-rhamnosides, which gave the C-methylated L-and Didopyranosides (2 and 2') in 48% overall yield in 5 steps. The synthesis of the segment 9 began with conversion of 2 into the alcohol 34) (60%; [oJD -6.9') in 4 steps: benzylation (BnBr/n-B@lI/NaI-I/THF), hydrolysis (HCl/aq. dioxane) to give an idose derivative, NaBHq (MeOH) reduction to afford a free diol, and selective 0-silylation fTBDPS-C1/imidaz.ole/DMF). PCr _ddation (MS 3A/CH2C12) of 3 afforded the methyl ketone 44) (99%; [oJ~+ll"). This was transformed into the olefin S4) (75%; [c&+10") according to a Shapiro's method5) by reaction with tosylhydrazide (THF, 67h) to give the corresponding hydrazone followed by treatment with n-butyllithium (hexane/THF, 2h). Ozonolysis of 5 with reductive workup (03/MeOH, -78'C, lmln; then, CMeO)3P) gave the C-5 aldehyde, which was subjected to