Tylonolide tylosin aglycon

Since tylosin is composed of tylonolide (macrolactone aglycone ring) and three attached sugars having several chemically reactive hydroxyl groups, it is... 

Diisopinocampheylborane is not an effective asymmetric hy-droborating agent for 2-substituted 1-alkenes. High selectivities have, however, been achieved where one of the substituents is very bulky. This aspect has been elegantly demonstrated by the synthesis of both enantiomers of a precursor of tylonolide, the aglycone of tylosin, which is one of the members of the polyoxomacrolide antibiotics. In both cases the isomeric ratio was at least 50 1 (eqs eq 8 and eq 9). ... 

As is the case for the leucomycin group, several aglycones exist in the tylosin group winch differ in the pattern of oxidation and substitution of the lactone. If the aglycone contains an aldehyde, cleavage of the aminosugar yields the hemiketal, such as tylonolide and rosaranolide. 

Tylonolide hemiacetal (33), the aglycone of the antibiotic tylosin, possesses an anti 14-hydroxymethyl-15-acyloxy stereochemistry conveniently contained in 26, which may be viewed as the western half of 33. In order to prepare the eastern half of 33, an aldol reaction leading to the desired syn stereochemistry at C-3 and C-4 is exploited. The reaction of achiral aldehyde 27 with the S-boron enolate 28 proceeds with the expected diastereofacial selectivity to provide, in a combined yield of 80% after O-silylation, a separable mixture of 29 (derived from the / -enantiomer of 27) and 30 (from the S-enantiomer of 27). Subsequent functional group transformation of 30 ultimately leads to the a-(TMS)methylketone 31. The anion of 31, generated with lithium hexamethylsilazide in THF at — 78 °C, undergoes a Peterson condensation with 26 to afford in 60% yield the seco-diC d 32. Treatment of 32 with 70% acetic acid at 85 °C for one hour affords 33 in 60% yield. The attractive feature of this... 

Tvlosin. The derivative (100b) of tylonolide hemiacetal (100a), an aglycone of the macrolide antibiotic tylosin (cf. 1, 153), has been synthesized... 

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