Cne approach to the total synthesis of clinically interesting m@ansinoidsl 1 relies on closure of the macrocyclic ring at the Cl -N peptide bond. To be preparatively usefuI any plan of this nature requires the smooth stereospecific assembly of an sppropriate acyciic precursor, consequently we have devised a convergent scheme which employs C9 as a connecting point for suitably protected Cl-C8 sml Cl0 -C21 fragments. This Letter describes our coupling method, based on tie principle of %mpole*, and details the subsequent elaboration of maytansine's csrblnolamide functionality In a represeptetive model system 18 2 -* CH30 1 R= -CO-7%CH3 I-I c/"\ 3 cCC% Retrosynthetic analysis suggests that the six-membered carbamate in 1 might be formed b intramolecular interception of a C9 isocyanate with an hydroxyl substituent at C7 of 2. Precedents exist for this type of cyclization during the Curtius rearrangement of y-hydroxyacid hydraxides. 3, 2c Inthecsse of maytansine, the appropriate a, y-dihydroxyacid synthon in 2 can be imagined to arise from the condensation of C9 glycolate fragment 3 a C/-C8 epoxide 5, and a Cl0 aldehyde A. With current improvements in the Curtius and Lossen rearrangements, 4 these VUmpolu~l transformations can be achieved under very mild, near-neutral conditions which are compatible with maytansine~s sensitive functionality.