[91]. Later, they further improved the total synthesis and also reported a secondgeneration total synthesis of CTX3C in which the penultimate step involved a
RCM-mediated construction of the central eight-membered O-ring [92]. The formation of the eight-membered E- and I-rings was carried out by RCM. Moreover,
once the ABCDE-ring system and the HIJKLM-ring system were synthesized, the
total synthesis was accomplished by the union of both segments by construction of
the F-ring through a RCM.
Other groups have reported elegant total synthesis of CTX3C. Thus, Clark
et al. have disclosed a relatively short and efficient approach to the synthesis of the
pentacyclic ABCDE fragment of CTX3C in which two-directional and iterative
RCM were used to effect the ring construction [93]. Kadota et al. achieved a
convergent synthesis of the A–E-ring segment of ciguatoxin CTX3C via the intramolecular allylation of a chloroacetoxy ether and a RCM using the second-generation
Grubbs catalyst to construct ring E [94]. Recently, this group has developed a
convergent synthetic route to the HIJKLM-ring system of ciguatoxin CTX3C. The
key transformations were a conjugate addition/alkylation, spiroacetalization, intramolecular allylation, and finally RCM, followed by a stereoselective hydrogenation,
where the RCM was carried out with the Hoveyda–Grubbs second-generation catalyst to provide the corresponding cyclized I-ring [95]. Fujiwara et al. also described
an efficient synthesis of the IJKLM-ring part of ciguatoxin CTX3C [34]. Their
synthesis also featured a RCM as the key step, but at an earlier stage.
Brevetoxin A (Fig. 4) is a decacyclic ladder toxic metabolite of Karenia brevis
possessing five-, six-, seven-, eight-, and nine-membered oxacycles, as well as
22 tetrahedral stereocenters. This compound is known to cause the infamous red
tide phenomenon responsible for massive fish kills, as well as neurotoxic shellfish
poisoning and bronchial irritation in humans. Crimmins et al. have developed a
unified approach to the construction of the B-, E-, G-, and J-rings based upon a
Scheme 15 Synthesis of the cyclopropyl lactone of solandelactone 92 developed by Varadarajan
et al.
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E. Soriano and J. Marco-Contelles
RCM-mediated construction of the central eight-membered O-ring [92]. The formation of the eight-membered E- and I-rings was carried out by RCM. Moreover,
once the ABCDE-ring system and the HIJKLM-ring system were synthesized, the
total synthesis was accomplished by the union of both segments by construction of
the F-ring through a RCM.
Other groups have reported elegant total synthesis of CTX3C. Thus, Clark
et al. have disclosed a relatively short and efficient approach to the synthesis of the
pentacyclic ABCDE fragment of CTX3C in which two-directional and iterative
RCM were used to effect the ring construction [93]. Kadota et al. achieved a
convergent synthesis of the A–E-ring segment of ciguatoxin CTX3C via the intramolecular allylation of a chloroacetoxy ether and a RCM using the second-generation
Grubbs catalyst to construct ring E [94]. Recently, this group has developed a
convergent synthetic route to the HIJKLM-ring system of ciguatoxin CTX3C. The
key transformations were a conjugate addition/alkylation, spiroacetalization, intramolecular allylation, and finally RCM, followed by a stereoselective hydrogenation,
where the RCM was carried out with the Hoveyda–Grubbs second-generation catalyst to provide the corresponding cyclized I-ring [95]. Fujiwara et al. also described
an efficient synthesis of the IJKLM-ring part of ciguatoxin CTX3C [34]. Their
synthesis also featured a RCM as the key step, but at an earlier stage.
Brevetoxin A (Fig. 4) is a decacyclic ladder toxic metabolite of Karenia brevis
possessing five-, six-, seven-, eight-, and nine-membered oxacycles, as well as
22 tetrahedral stereocenters. This compound is known to cause the infamous red
tide phenomenon responsible for massive fish kills, as well as neurotoxic shellfish
poisoning and bronchial irritation in humans. Crimmins et al. have developed a
unified approach to the construction of the B-, E-, G-, and J-rings based upon a
Scheme 15 Synthesis of the cyclopropyl lactone of solandelactone 92 developed by Varadarajan
et al.
334
E. Soriano and J. Marco-Contelles