Decarestrictine D

Four new decarestrictine analogues (botryolides A-D; 1- 4), a biosynthetically related gamma-lactone (botryolide E; 5), and the known compounds decarestrictine D ( 6) and sterigmatocystin have been isolated from cultures of a fungicolous isolate of Botryotrichum sp. (NRRL 38180). The structures of these compounds were determined by analysis of 2D NMR and ESIMS data. The relative configurations of 1- 5 were established on the basis of NMR data and/or X-ray diffraction analysis, while the absolute configuration of 1 was assigned using the modified Mosher method.

[reaction: see text] The core structure of decarestrictine D was constructed by stereoselective oxygenation of (2Z,4E)-alkadienyl alcohol, which could be synthesized by a nickel-catalyzed coupling reaction between the corresponding cis bromide and trans borate. Efficiency in macrocyclization of the seco acid with Yamaguchi reagent was found to be protective-group-dependent, and the best yield of 40% was obtained with the seco acid with tri-MOM protective groups.

The 3-alkene-1,2,5-triol structure is not only a major framework of biologically important molecules but also a new functional-group-rich unit for synthesis of polyols and sugars. A method furnishing such triol derivatives 8 was developed and successfully applied to synthesis of decarestrictine D (18). First, coupling reaction of the unprotected alcohols 2 with borates 4 was investigated to produce the dienyl alcohols 6 with NiCl2(dppf) in Et2O/THF (5:1) at room temperature. The hydroxyl-group-directed epoxidation of 6 followed by palladium-catalyzed reaction with AcOH (Scheme 1) furnished 3-alkene-1,2,5-triol derivatives 8. Since each step proceeded with high stereo- and regioselectivities, the stereochemistry of 8 has been correlated with the olefin geometry of 6. With the above transformation in mind, synthesis of the full carbon skeleton of decarestrictine D (18) could be designed easily and was completed successfully. Furthermore, a new seco acid 19b with the MOM protective group for the three hydroxyl groups was found to afford macrolide 48 in a yield higher than those reported previously.