Good timing in total synthesis: the case of phoslactomycin A.
The importance for the right order of functional group introduction and manipulation (good timing) was demonstrated in the course of a total synthesis of phoslactomycin A. The synthetic strategy comprised a Cu(I)-thiophene carboxylate (CuTC, Liebeskind's reagent)-mediated coupling to introduce the Z,Z-diene at the final stage of the synthesis in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-aldol reaction and an advanced protective group strategy. The C14-C21 fragment was accessible via an asymmetric 1,2-addition to cyclohexenone and a subsequent diastereoselective ketone reduction. One crucial task was the dihydroxylation of the C8-C9 alkene, the introduction of the C6-C7 double bond and the generation of the C25-nitrogen functionality. A second example consisted of the best sequence for the generation of the functional groups in the core part (first phosphorylation, second iodo-olefination, third azide/carbamate conversion). The synthetic solutions from this approach are compared with the already existing contributions in the phoslactomycin area.
Gebhardt
Björn
B
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
König
Christian M
CM
Schleth
Cornelia
C
Dauber
Mario
M
Koert
Ulrich
U
D000475:Alkenes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry; D002384:Catalysis; D007202:Indicators and Reagents / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones; D013237:Stereoisomerism
D000475:Alkenes; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001386:Azides; D001688:Biological Products; D002219:Carbamates; D007202:Indicators and Reagents; D007783:Lactones; D009943:Organophosphorus Compounds; D011753:Pyrones; C060448:phoslactomycin A