Total Synthesis Highlights

The convergent coupling of 1 with 2 was carried out under Suzuki conditions. Reduction of the
iodide of 2 to the corresponding alkyl lithium followed by exchange with B-OMe-9-BBN gave
gave an intermediate organoborane, that smoothly coupled with 1 under Pd catalysis to give 18.
Deprotection and carbamate formation then led to (+)-discodermolide (3).
This synthesis clearly illustrates the power of 5 as an enantiomerically-defined secondary
organometallic reagent, and the synthetic versatility of the product alkenyl carbamates. The ready
availability of the three enantiomerically-pure four-carbon fragments 4, 8, and 14 was also a key
consideration in the design of this synthesis.
37. The Maier Synthesis of Cruentaren A
Cruentaren A (3), isolated from the myxobacterium Byssovorax cruenta, is an inhibitor of
mitochondrial F-ATPase. The synthesis of 3 (Org. Lett. 2007, 9, 655,; Angew. Chem. Int. Ed. 2007,
46, 5209.) by Martin E. Maier of the Universität Tübingen illustrates the power of alkyne
metathesis as a tool for the synthesis of complex natural products. Very recently, Alois Fürstner of
the Max-Planck-Institut, Mülheim, reported (Angew. Chem. Int. Ed. 2007, 46, 9275.) an
alternative synthesis, also based on alkyne metathesis, of cruentaren A (3).
The alcohol portion of 1 was prepared by Marshall homologation of 4 with 5, leading to 6.
Homologation of the derived epoxide 7 then gave 8. Note that the homologation of 7 to 8 required
three steps. This might have been accomplished more directly with the Li salt of 1-propyne, easily
prepared from commercial 1- or 2-bromopropene.