Total synthesis of 10-deoxymethynolide and narbonolide.
A flexible and convenient approach was developed for the synthesis of 10-deoxymethynolide (1) and narbonolide (2), which are aglycones of the methymycin and the pikromycin families of macrolide antibiotics. These lactones are produced by pikromycin polyketide synthase from Streptomyces venezuelae. Polyketide lactones, 10-deoxymethynolide and narbonolide, which contain 12- and 14-membered rings, respectively, were synthesized efficiently. These target lactones were retrosynthetically divided into three parts and assembled by using an asymmetric aldol reaction, the Yamaguchi esterification, and ring-closing metathesis. The ring-closing metathesis reaction catalyzed by the second-generation Grubbs catalyst is particularly efficient in preparing these macrocyclic polyketide lactones.
Xuan
Richeng
R
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.
Oh
Hong-Se
HS
Lee
Younghoon
Y
Kang
Han-Young
HY
D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D048630:Polyketide Synthases / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013302:Streptomyces / Q000201:enzymology
D007783:Lactones; D018942:Macrolides; C517337:narbonolide; D048630:Polyketide Synthases; C079477:10-deoxymethynolide