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Synthesis of the C19-truncated maltepolide E has been accomplished via a diene–ene RCM strategy without damage to the C11–C14 alkenyl epoxy unit. Upon release of the C17-OH group, it attacked at the C14 position with double bond migration and epoxide ring-opening to furnish the C19-truncated maltepolide A and B as proposed for the biosynthesis of maltepolides. Preliminary cytotoxicity data of the synthesized C19-truncated maltepolides against L929 mouse fibroblast cell line suggest irrelevance of the vinyl epoxide and importance of the conjugated dienyl keto unit for the observed anticancer activity.

The fully substituted C17–C30 bis-tetrahydrofuran fragment of the proposed structure of iriomoteolide-13a has been assembled via asymmetric dihydroxylation-SN2 cyclization of 19-mesyloxy-21-ene-26-yne and PdCl2-catalyzed syn-oxypalladation of 26-ene-17,21,23,28-tetraol as the key steps. The syn-oxypalladation process gave an 89:11 diastereoselectivity and tolerated the free poly-hydroxy groups in the highly functionalized substrate.

The C19–C30 bis-THF fragment of the proposed structure of iriomoteolide-13a has been synthesized. The ω-mesyloxy-substituted stereotetrad possessing three continuous hydroxy groups was generated by an anti-aldol reaction and asymmetric dihydroxylation (AD) as the key steps. Upon heating in pyridine, the stereotetrad underwent an SN2 cyclization to form the C19–C22 THF ring chemoselectively. The propargylic alcohol, after cleavage of the C28-OPMB ether, was reduced to the corresponding allylic alcohol with spontaneous removal of the C23-OTBS protecting group. Finally, the ene triol was subjected to the Pd(II)-catalyzed intramolecular syn-oxypalladation to give the C23–C26 THF ring with a dr value of 86 : 14. It was found that the C21-OH group, which might form a chelated Pd(II) complex along with the C23-OH group, was tolerated during the syn-oxypalladation process.

The C19–C30 bis-THF fragment of the proposed structure of iriomoteolide-13a has been synthesized. The w-mesyloxy-substituted stereotetrad possessing three continuous hydroxy groups was generated by anti-aldol reaction and asymmetric dihydroxylation (AD). Upon heating in pyridine the stereotetrad underwent an SN2 cyclization to form the C19–C22 THF ring. It was followed by an intramolecular syn-oxypalladation of the C28 chiral allylic alcohol to give the C23–C26 THF ring.

The C19–C30 bis-THF fragment of the proposed structure of iriomoteolide-13a has been synthesized. The w-mesyloxy-substituted stereotetrad possessing three continuous hydroxy groups was generated by anti-aldol reaction and asymmetric dihydroxylation (AD). Upon heating in pyridine the stereotetrad underwent an SN2 cyclization to form the C19–C22 THF ring. It was followed by an intramolecular syn-oxypalladation of the C28 chiral allylic alcohol to give the C23–C26 THF ring.