Studies on Synthesis of the Antibiotic Nosiheptide

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12640526
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: IWAKI MEISEI UNIVERSITY
• Principal Investigator: UMEMURA Kazuyuki IWAKI MEISEI UNIV., Sciences and Engineering, Assistant Professor, 理工学部, 講師 (90221811)
• Project Period (FY): 2000 – 2001
• Keywords: Nosiheptide / Antibiotic / Fragment A / Thiostorepton

Research Abstract

A polythiazole antibiotic, nosiheptide, is composed of heterocyclic fragments C, D, E, A, L-threonine, and dehydroalanine. For a total synthesis of nosiheptide, we have already reported the syntheses of fragments C, D, E, and their peptides. A fragment A derivative can be obtained as a stable compound by acid hydrolysis of the antibiotic, so that 6-{2-[1-(t-butoxycarbonylamino)-2-(p-methoxy-benzylthio)ethyl]-4-thiazolyl}-3-ethoxy-2, 5-bis (4-ethoxycarbonyl-2-thiazolyl) pyridine might be useful as its building block. Thus, we herewith describe the synthesis of fragment A in detail. Similar fragment derivatives of antibiotic micrococcin P and sulfomycin, micrococcinic acid and dimethyl sulfomycinamate, have been recently synthesized using the palladium-catalyzed reaction by cross-coupling between the pyridine and thiazole rings. However, both fragment derivatives are unstable under the conditions of the acid hydrolysis, and the yield for this cross-coupling reaction is not sufficiently high. Therefore, they can not be used for the total synthesis. From the considerations of the stability for the building block and the yield during its formation, we have chosen a stepwise construction method.