Synthesis of the Functionalized Tricyclic Skeleton of Guanacastepene A: A Tandem Epoxide-Opening β-Elimination/Knoevenagel Cyclization This work was supported by the National Institutes of Health (HL-25848 and CA-28824). D.S.T. is a Damon Runyon Cancer Research Foundation postdoctoral fellow (DRG-1641). G.B.D. is an NIH postdoctoral fellow (1 F32 NS11150-01). We thank Dr. George Sukenick and Sylvi Rusli (NMR Core Facility, CA-02848) for mass spectral analyses.

Abstract

Der Ring ist geschlossen! Die ernsthaften Probleme, die der Ringschluss zur Kerneinheit von Guanacastepen A 1 aufwarf – insbesondere die der unterschiedlichen Oxidationszustände von C14 und C15 –, ließen sich erfolgreich lösen (siehe Schema). Obwohl noch nicht verallgemeinert, sollte die vorgestellte Methode für breitere Anwendungen beim Aufbau inkrementell oxygenierter polycyclischer Naturstoffe geeignet sein.

Cyclohexyne Cycloinsertion in the Divergent Synthesis of Guanacastepenes

“…Acylation of 64 provided 66 , which showed a 1 H NMR proton coupling constant of the C13 proton of 11.8 Hz. This value is consistent with a C13‐α‐configuration 7a. Notably, the stereoinduction in the hydroxylation step is contrary to that obtained in procedures previously described for the introduction of the C13 hydroxyl by epoxidation of a similar silyl enol ether, which furnished the β‐hydroxide in d.r.…”

“…Notably, the stereoinduction in the hydroxylation step is contrary to that obtained in procedures previously described for the introduction of the C13 hydroxyl by epoxidation of a similar silyl enol ether, which furnished the β‐hydroxide in d.r. of 9:1 7a,d,f. The use of other silyl groups (TMS, TES) or employment of a mixed C14‐TES/C15‐TBS‐enol ether resulted in a faster reaction but diminished yields.…”

“…Pioneering work in this field has been carried out by Danishefsky, who disclosed the total synthesis of guanacastepene A ( 1 ) in 2002 7a,b. The effective strategy for assembly of the tricyclic carbon core involved functionalization of an A‐ring building block followed by alkylation and cyclization to construct the A–B hydroazulene (Scheme , strategy I).…”

A Stereoselective Route to Guanacastepene A through a Surprising Epoxidation This work was supported by the National Institutes of Health (CA-28824). S.L. is a US Army breast cancer research program postdoctoral fellow (DAMD-17-99-1-9373). G.B.D. is an NIH postdoctoral fellow (1 F32 NS11150-01). D.S.T. is a Damon Runyon Cancer Research Foundation postdoctoral fellow (DRG-1641). We thank Dr. George Sukenick and Sylvi Rusli (NMR Core Facility, CA-02848) for mass spectral analyses.

“…In the preceding paper we reported the preparation of compound 3 (Scheme ),1 which bears much of the functionality required, in principle, to reach guanacastepene A ( 1 ) 2, 3. To complete the synthesis,4 it would be necessary to reproduce, through chemical synthesis, the densely packed and varied functionality between C13 and C5.…”