10.1 12-Membered Macrocyclic Lactones
10.1.1 (+)-10-Deoxymethynolide
(+)-10-Deoxymethynolide
132,
the
12-membered
aglycone
of
10-deoxymethymycin, was efficiently constructed via an intramolecular
Nozaki–Hiyama–Kishi coupling reaction. Therefore, aldehyde 130 was treated
with excess of CrCl 2 (10.7 equivalent) containing about 2 % of NiCl 2 affording a
1/1 mixture of diastereomeric allylic alcohols 131, in 74 % yield [82] (Scheme 34).
Notably the stereochemistry at C7 had no consequence for the total synthesis of
(+)-10-deoxymethynolide 132, as the epimeric mixture of 131 was oxidized in the
next step.
10.2 13-Membered Macrocyclic Lactones
10.2.1 (+)-Brefeldin C
The intramolecular NHK coupling reaction has also been utilized to generate
13-membered lactone 135 although with less useful levels of diastereoselection.
Subjection of 133 to typical NHK conditions provided a 4/l mixture of 134 and the
desired natural product (+)-brefeldin C 135 in 60 % yield [83] (Scheme 35).
Scheme 34 Construction of 12-membered lactone 131 via intramolecular Nozaki–Hiyama–Kishi
(NHK) coupling
Synthesis of 12- to 16-Membered-Ring Lactones
397