Totally Synthetic by Paul H. Docherty, 7 June 2006
Total Synthesis of SCH 351448
M. T. Crimmins, G. S. Vanier, Org. Lett. 2006, 8, 2887-2890.
A dimeric beast, Crimmins and Vanier have completed the total synthesis of the natural product named SCH 351448 with a demonstration of some of the most powerful and useful synthetic methods in organic synthesis. A popular target (with three previous syntheses), their work was completed in 30 steps (LLS - longest linear sequence), generating the only known selective activator of LDL-R (low-density lipoprotein receptor). All but two of the stereocenters were established through chiral enolate reactions, demonstrating deft usage of a variety of chiral auxiluaries and aldol chemistry. Especially useful was the use of Ti enolatates. They also performed six alkene metatheses, including three in the following impressive transformation:
The different auxiliaries give different stereochemical results. The ones with a C=S bond give “non-Evans” syn aldols and are more easily cleaved. For the simple alkylations, you need the classic Evans oxazolidinone auxiliary.
But does anyone know why they chose to use 5 different kinds of auxiliaries? (the acetate aldol one is immediately understandable…)