Of pikronolide

Chakraborty, T. K. Das, S. Synthesis of chiral 1,3-diols by radical-mediated regioselective opening of 2,3-epoxy alcohols using Cp2TiCl2. Tetrahedron Lett. 2002, 43, 2313-2315. Nakajima, N. Tanaka, T. Hamada, T. Oikawa, Y. Yonemitsu, O. Highly stereoselective total synthesis of pikronolide, the aglycon of the... 

Pikromycin. Pikromycin (19, R = OH, R = H), the first macrolide discovered (77,78), is produced by S.felleus. Pikromycin is identical to amaromycin and albomycetin (79—81) and may be identical to proactinomycin (82—84). The structure of pikromycin was determined from chemical degradation, mass spectrometry, nmr, and x-ray crystallography (85-90). Its aglycone, pikronolide (20, R = OH), was produced by S. vene uelae (36). A derivative, kromycin (22, R = OH), was formed from pikromycin under acidic conditions (87,88,91) and more drastic conditions produced an intramolecular spiroketal of pikronolide named kromin (89,91). 10,11-Dihydropikromycin (21, R = OH, R = H), was also produced by S. vene uelae (92). 

The additional presence of a 3-methoxy substituent on the benzyl group confers greater stability on the intermediate cation, and consequently oxidation of DMPM ethers by DDQ is even more facile. Yonemitsu and cowoikers have used this differential reactivity of substituted benzyl ethers to great effect in the total synthesis of the macrolide antibiotics methynolide, tylonolide, (95)-9-dihydroerythro-nolide and pikronolide. The pikronolide synthesis provides an excellent example of the selective, sequential deprotection of DMPM, MPM and benzyl ether protecting groups (Scheme 7). 

Yonemitsu s pikronolide synthesis is based on the coupling of the C -Ciq (123) and C11-C13 (30) segments derived from D-glucose, and the effective application of benzyl type protecting groups, MPM (4-methoxybenzyl) and DMPM (3,4-dimethoxybenzyl), which were developed by his group for the macrolide synthesis. 

---