Total Synthesis of (+)-Zaragozic Acid C

Key words

(+)-zaragozic acid C - squalestatin 1 - heterotrimerization - Brook rearrangement - aldol addition

Significance

Johnson and co-workers present a rapid synthesis of (+)-zaragozic acid C, a highly oxygenated polyketide featuring a dioxabicyclo[3.2.1]octane bearing six contiguous stereocenters. The natural product, also known as squalestatin 1, is a potent inhibitor of the squalene synthase which is responsible for cholesterol production.

Comment

1,2-Addition of vinyl Grignard B to silyl glyoxylate A triggers a controlled trimerization which is terminated with the addition of ketene acetal E into glyoxylate C. This sequence is highly efficient. Triacetate L is thus promptly accessed, enabling the synthesis of (+)-zaragozic acid C.

Publication History

Article published online:
13 March 2024