59(P28) チオペプチド系抗生物質ミクロコッシンPの全合成(ポスター発表の部)

抄録

Micrococcin P (1), isolated from the culture of Bacillus pumilus, is a unique macrocyclic peptide. In addition, many similar antibiotic peptides have been also isolated from various kinds of strains. The peptide (1) include a characteristic main structure, 2,3,6-polythiazolesubstituted pyridine skeleton called Fragment A-C (11) composed of multisubstituted pyridine and thiazole-dehydropeptide moieties and two segments, Fragments B and D. First of all, the protected Fragment A-C segment (11) was synthesized from 3-cyano-6-dimethoxymethyl-2-pyridone via 2-bromoacetyl-3-(5-ethoxycarbonyl)-thiazole-6-dimethoxymethylpyridine(9) in twelve steps. Furthermore, the protected Fragment D (17) was obtained from N,O-Isop-Thr-OH (14) via the corresponding N,O-Isop-Thr-propanolamide (15) in four steps. On the other hand, the protected Fragment B (21) was also synthesized from N, O-diprotected Thr-[1- propen-1-yl]thiazole-4-carboxylate (18) in three steps. Finally, after the coupling of Fragment A-C (11) with Fragment D (17) and then Fragment B (21), the obtained linear precursor Fragment A-B-C-D of 1 was cyclized using BOP and deprotected with TBAF to give micrococcin P.