Total synthesis of carbomycin B and josamycin (leucomycin A3)

Macrolactonizations in the Total Synthesis of Natural Products

“…Several other syntheses have been reported: methynolide with (CF 3 CO 2 ) 2 Hg; 138 carbomycin/josamycin, 146 cytochalasins, 109 lactone antibiotic A26771B, 147 and chlorothricolide 148 with CF 3 CO 2 Ag; deoxyerythronolide 142 and crobarbatine acetate 149 with CuOTf-benzene complex; and tylonolide 150 with (CF 3 CO 2 ) 2 Hg. Nonmetallic additives such as NBS 151,152 and p-TsOH 73 proved to be useful in these reactions.…”

Carbohydrate-Based Macrolides Prepared via a Convergent Ring Closing Metathesis Approach: In Search for Novel Antibiotics

“…Modifications include acylation of hydroxy groups, deacylation, aldehyde or ketone reduction, double bond reduction, and N-demethylation . More fundamental structural changes require synthesis of macrolide analogues from simple building blocks, and over the past few years four general approaches have been developed to control the critical stereochemistry: (i) ring-cleavage, where the appropriate stereorelationship of the asymmetric centers is first secured by using the conformational bias of a small or medium sized ring, which is then opened to give an acyclic fragment with the stereocenters correctly related, (ii) exploitation of the existing asymmetric centers and functionalities of a carbohydrate precursor, (iii) stereoselective introduction of new asymmetric centers on an acyclic precursor, and (iv) stereoselective introduction of new asymmetric centers onto an intact macrocyclic precursor, using the conformational bias of the macrocycle . Additional problems in the total synthesis of macrolide analogues are the macrolactonization step and the stereo- and regiocontrolled attachment of the appropriate basic or neutral deoxysugars.…”

Update 1 of: Macrolactonizations in the Total Synthesis of Natural Products

“…For example, using silver trifluoroacetate in buffered benzene 156,157 (Scheme 16), this methodology was particularly useful in the aplysiatoxin 156 total synthesis, which involves a sensitive substrate prone to crotonization under basic conditions. Several other syntheses have been reported: methynolide and tylonolide 158 with (CF 3 CO 2 ) 2 Hg; 150 carbomycin/josamycin, 159 cytochalasins, 120 lactone antibiotic A26771B, 160 and chlorothricolide 161 with CF 3 CO 2 Ag; deoxyerythronolide 154 and crobarbatine acetate 162 with CuOTf−benzene complex; and the macrocyclic core of galbonolides 163 with Hg(OAc) 2 .…”