Total Synthesis of Aplysiasecosterol A

Aplysiasecosterol
A (1) is a structurally unusual
9,11-secosteroid isolated from the sea hare Aplysia
kurodai. We have accomplished the first and asymmetric
total synthesis of 1 in a convergent fashion. The left-hand
segment bearing three adjacent stereocenters was constructed through
desymmetrizing reduction, ketalization, and radical cyclization. A
strategy of asymmetric 2-bromoallylation followed by spontaneous desymmetrizing
lactolization enabled a more expeditious access to this segment. The
right-hand segment was prepared through two different approaches:
one featuring Myers alkylation and Suzuki–Miyaura coupling
and the other relying upon Aggarwal lithiation–borylation and
Zweifel–Evans olefination. The two fragments were coupled by
a Reformatsky type reaction. The three consecutive stereocenters embedded
in the central domain of 1 were generated by an iron-mediated,
hydrogen atom transfer based radical cyclization reaction.