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. 2023 Dec 22;29(72):e202303121.
doi: 10.1002/chem.202303121. Epub 2023 Nov 2.

Synthesis of the A-F Fragment of the Pacific Ciguatoxin CTX3C by Iterative Ring-Closing Metathesis and Tsuji-Trost Allylation

Myron Triantafyllakis  1 , Sam Alexander  1 , Sophie Woolford  1 , Claire Wilson  1 , J Stephen Clark  1
Affiliations

Synthesis of the A-F Fragment of the Pacific Ciguatoxin CTX3C by Iterative Ring-Closing Metathesis and Tsuji-Trost Allylation

Myron Triantafyllakis et al. Chemistry. .

Abstract

The fully functionalized A-F fragment of the Pacific ciguatoxin CTX3C has been synthesized from a derivative of D-glucal, which serves as the B-ring. Rings A and C were introduced to either side of ring B by ring-closing diene and enyne metathesis (RCM). The seven-membered D-ring and eight-membered E-ring were assembled by iterative use of a six-step reaction sequence in which RCM was used for ring construction and Tsuji-Trost allylation was employed for subsequent stereoselective functionalization. The nine-membered F-ring was formed by use of an RCM reaction and bears the functionality required for attachment of the I-M fragment and subsequent closure of rings G and H.

Keywords: Tsuji-Trost allylation; ciguatoxin; iterative ring construction; polyether; ring-closing metathesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative Pacific ciguatoxins.
Figure 2
Figure 2
Disconnection of CTX3 C into the A−F fragment ii and the I−M fragment iii.
Scheme 1
Scheme 1
Synthesis of the AB fragment from protected D‐glucal (1).
Scheme 2
Scheme 2
Two routes for elaboration of the triflate 7 to give the ABC fragment 11.
Scheme 3
Scheme 3
Functionalization of ring C to permit extension of the fused polycyclic ether array.
Scheme 4
Scheme 4
Installation of ring D by sequential RCM and stereoselective palladium‐mediated Tsuji–Trost allylation.
Scheme 5
Scheme 5
Installation of ring E by sequential RCM and stereoselective palladium‐mediated Tsuji–Trost allylation.
Scheme 6
Scheme 6
Construction of ring F to complete the A−F fragment of CTX3C.
See this image and copyright information in PMC

References

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