Convergent de novo synthesis of vineomycinone B2 methyl ester

Abstract

An efficient de novo synthesis of vineomycinone B2 methyl ester has been achieved. The longest linear route required only 14 steps from achiral commercially available starting materials (4.0% overall yield). The key transformations included the de novo asymmetric synthesis of two key fragments, which were joined by a convergent late stage Suzuki’s glycosylation for the construction of the aryl β-C-glycoside. A subsequent BBr3 one-pot debenzylation, demethylation and air oxidation provided vineomycinone B2 methyl ester.

Methods for 2-Deoxyglycoside Synthesis

“…Expanding on their Pd(0)-catalyzed de novo synthesis of oligosaccharides, 347 the O’Doherty group 376 also developed a convergent de novo strategy starting from achiral acylfuran 371 and anthrafuran 373 for the synthesis of vineomycinone B2 methyl ester 375 , a secondary metabolite of the anthracycline antibiotic vineomycine B2 ( Scheme 101 ). The two key fragments 372 and 373 were coupled by a Suzuki’s glycosylation to give the aryl β- C -glycoside.…”

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

“…The usefulness of the protocol implemented by O’Doherty’s group from achiral furan 157 via enantioselective reduction, Achmatowicz ring-expansion, and diastereoselective (iterative) palladium-catalyzed glycosylation(s) has been further demonstrated with the successful synthesis of anthrax tetrasaccharide ( 171 ) [145,146,147], the trisaccharide portion of landomycin A ( 172 ) [148], cleistroside-2 ( 173 ) and several members other members of the cleistroside (tri- and tetra-rhamnosides) family [149], as well as the total syntheses of kaempferol glycoside SL101 ( 174 ) [150], jadomycin B ( 175 ) [151,152], and vineomycinone B 2 methyl ester ( 176 ) [153] (Figure 4) [154].…”

Recent Advances in C-Glycoside Chemistry: Application, Synthesis and Reactions

“…Para a síntese de Cglicosídeos inclui o acoplamento cruzado Suzuki, que envolve a reação entre ácidos aril/vinil-borônicos ou organoboranos e halogenetos arila/vinilo ou triflatos catalisados por complexos de paládio. [167][168][169][170][171][172][173] Os glicais halogenados ou os estanil-glicais atuam como substratos potenciais no acoplamento de Stille com organoestanho ou organohaletos para fornecer C-glicosídeos. [174][175][176][177][178][179][180] Por outro lado, C-glicosídeos também pode ser sintetizado pela reação de acoplamento de Negishi de um composto de organozinco ou um halogeneto orgânico, catalisado por complexos de níquel ou paládio.…”