ibid. 1982,486.70 -89. [S] X-ray crystal structure analyses: Siemens P4 four-circle diffractometer, Mo,,, radiation, I = 71.073 pm, scan mode w21B, T = 173(2) K, absorption correction DIFABS, structure solution: direct methods with SHELXS-86, refinement: full-matrix least-squares against a, refinement program SHELXL-93. hydrogen atoms geometrically positioned and refined with a riding model. 2: crystal dimensions 0.6 x 0.5 x 0.1 mm3, triclinic, space group P i , a = 715.60(10), b = 1243.3(2). c = 1387.7(2) pm, a = 105.490 (10), 0 = 96.330(10), y = 104.329(10)', V= 1.1321(3) nm', Z = 4 , pcalcd = 3.416 Mgm-', Om,, =27.50', 10436 measured reflections, 5137 unique (R,,, = 0,0752). absorption coefficient 8.130 mm-' , number of free parameters 237. final R value(l>2o1), R1=0.0600, wR2=0.1448. 3: crystal dimensions 0.7 x 0.3 x 0.3 mm', orthorhombic, space group Pbca, a = 1256.00(10), h=906.80(10), c=2874.4(3) pm, V=3.2738(6) nm3, Z = 8 , pcalid = 2.647 Mgm ?, B, , , = 27.48", 4137 measured reflections, 3142 unique (R,,,, = 0.0306). absorption coefficient 5.638 mm-', number of free parameters 170, final R value ( I > 200, R1 = 0.0387, wR2 = 0.0757. The crystallographic data (excluding structural factors) for the structures reported in this publication have been deposited as supplementary publication no. CCDC-100534 at the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road.central core of these molecules relying on an intramolecular Diels -Alder rea~tion.1~1 In preliminary studies designed to explore the feasibility of a strategy towards the total synthesis of the CP molecules involving a rhodium-catalyzed carbenoid generation and intramolecular trapping, followed by a divinylcyclopropane rearrangement141 and a radical cyclization (Scheme 1) the core 3 bTBS OPMB 0 divinylcyclopropane [3,3]-sigmatropic rearrangement carbenoid cyclopropanation OTBS OPMB 4Scheme 1. Retrosynthetic analysis of the CP core model system 3 A Novel Approach to the CP-225,917 and CP-263,114 Core** model system 3 was defined as a target. We wish to report here the execution of this strategy, which culminated in the construction of racemic 22 which has the opposite stereochemistry at the quaternary center.The naturally occurring substances 114 (1) and CP-225,917(2) possess intriguing molecular architecture,['] important biological properties, and an interesting mechanism of As inhibitors of squalene synthase and farnesyl transferase, these substances are attractive from the pharmaceutical point of view, particularly with regards to lowering cholesterol levels and to treating cancer. Isolated from an unidentified species of fungi, these compounds include within their structures a novel bicyclo[4.3.l]dec-l(9),4-dien-lO-one framework on-3 NOE to which a variety of substituents are attached. We have previously reported on an approach to the .COOH -COOH 1: CP-263,114 2: CP-225,917 for help with NMR spectroscopy and mass spectrometry. respectively.The synthesis ...