2,3-O-isopropylidene-D-glyceraldehyde 87 and based on a RCM of the dienoic
ester 91 was developed by Varadarajan et al. [88] (Scheme 15).
Finally, it should be noted that the RCM has been applied to the construction of
eight-membered oxocin scaffold in polycyclic systems. Some examples are detailed
below. In 1989, Yasumoto et al. determined the structure of ciguatoxin (CTX, 8a,
Fig. 1), a neurotoxic polycyclic ether produced by the marine dinoflagellate
Gambierdiscus toxicus [89]. To date, the structures of more than 20 congeners
including CTX3C 8b [90] were also determined. The complex structure consists of
five- to nine-membered polycyclic ether core (A-M rings) containing 30 chiral
centers, a 5,6-spiroacetal, and four double bonds, three hydroxyl groups, and five
methyl groups on the ether rings. The size and the structural and stereochemical
complexity have made them irresistible synthetic targets, providing a stimulus for
the development of many new reactions and strategies. The first total synthesis of
CTX3C 8b by Hirama et al. in 2001 has been achieved on the basis of a highly
convergent strategy featuring the chemoselective RCM as one of the key steps
Scheme 14 Synthesis of the eight-membered ring core of octalactins developed by Aird et al.
Synthesis of Eight- to Ten-Membered Ring Ethers
333
ester 91 was developed by Varadarajan et al. [88] (Scheme 15).
Finally, it should be noted that the RCM has been applied to the construction of
eight-membered oxocin scaffold in polycyclic systems. Some examples are detailed
below. In 1989, Yasumoto et al. determined the structure of ciguatoxin (CTX, 8a,
Fig. 1), a neurotoxic polycyclic ether produced by the marine dinoflagellate
Gambierdiscus toxicus [89]. To date, the structures of more than 20 congeners
including CTX3C 8b [90] were also determined. The complex structure consists of
five- to nine-membered polycyclic ether core (A-M rings) containing 30 chiral
centers, a 5,6-spiroacetal, and four double bonds, three hydroxyl groups, and five
methyl groups on the ether rings. The size and the structural and stereochemical
complexity have made them irresistible synthetic targets, providing a stimulus for
the development of many new reactions and strategies. The first total synthesis of
CTX3C 8b by Hirama et al. in 2001 has been achieved on the basis of a highly
convergent strategy featuring the chemoselective RCM as one of the key steps
Scheme 14 Synthesis of the eight-membered ring core of octalactins developed by Aird et al.
Synthesis of Eight- to Ten-Membered Ring Ethers
333