Callophycoic acid A (1) was isolated by Kubanek and co-workers in 2007 from extracts of the red alga Callophycus serratus (Solieriaceae), which was collected near Cakau-i-Ra Reef, Fiji. This natural product is the first example of diterpene–benzoic acid in macroalgae. The structure is characterized by a brominated tricyclic skeleton containing an all-carbon quaternary stereocenter. It showed antibacterial activity against vancomycin-resistant Enterococcus faecium as well as antimalarial activity and cytotoxicity against human cancer cell lines. Interested in these features, we have been involved in synthetic studies of 1. In order to develop a method for construction of the all-carbon quaternary stereocenter in 1, we examined allylboration reaction of sugar-derived aldehydes. The reaction of D-glyceraldehyde derivative 2 or D-erythrose derivative 5 with geranylboronate 3 proceeded diastereoselectively, giving the γ-adduct possessing a quaternary stereocenter. This method was applied to the stereoselective synthesis of homoallylic alcohol 9-D from D-xylose derivative 7. By using boronate 8 instead of 3, higher diastereoselectivity was achieved. The γ-adduct 9 was converted into disubstituted olefin 12, which possesses the benzoic acid moiety. Then 12 was transformed to alkenyl bromides 19 and 20, and radical cyclizations were attempted to construct the cyclohexane ring. When triacetate 20 was used as the substrate, the desired cyclized product 21-a was preferentially obtained.
