Synthesis of the C1-C15 Region of Palmerolide A Using Refined Claisen-Type Addition-Bond Cleavage Methodology

Abstract

Synthesis of the eastern hemisphere (C1-C15) of pal­merolide A is described. A re-optimized Claisen-type condensation of vinylogous acyl triflates provides efficient entry into the C1-C8 subunit, setting up a convergent Horner-Wittig olefination to deliver the eastern portion of palmerolide A.

Key words

vinylogous acyl triflate - fragmentation - total synthesis - palmerolide - methodology

References and Notes

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3

Information available through the Antarctic Treaty Secretariat: http://www.ats.aq/.

5

Of the NCI’s panel of 60 cancer cell lines, no other cell
line registered a cytotoxic response below micromolar concentrations.

13

See Supporting Information, compound A.

17

See Supporting Information, compound B.

18

Cyclization of 5 predominated using bases including Ba(OH)₂, DBU˙LiCl (Masamune-Roush conditions), and KOt-Bu. A common feature of these bases is that each is intermediate in basicity between the initial β-keto phosphine oxide anion and the enolate arising from undesired cyclization onto the enoate. Therefore, the conjugate acid may play a role in promoting undesired cyclization (Scheme  [³] ).

20

See Supporting Information, compound C.