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In summary, a synthetic route to the potent cytotoxic
macrolide iejimalide B (1) has been established which
provides this valuable marine natural product in sufficient
quantity for further testing.As evident from this and the
preceding Communication,[4] the development of the success-
ful route required several rounds of adjustment and fine
tuning.This struggle largely originated from the exceptionally
low level of homology in the behavior of seemingly closely
related compounds that differed only in remote and osten-
sibly innocent substituents.The gathered intelligence, how-
ever, should provide a sound basis for the next round of
exploration of this promising lead structure.We are currently
extending our studies to the other members of this family and
translating the acquired knowledge to the design of potential
analogues with optimized application profiles.
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Keywords: anticancer agents · cross-coupling · macrolides ·
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[19] This route to 27 was chosen for two reasons: first, problems with
partial racemization were encountered when the aldehyde
derived from 23 was treated with Wittig reagents in an attempt
to form 28 directly; secondly, it is known that iejimalide B
bearing a methyl group at C2 is more active than iejimalide A
which features a proton at this position, see Ref.[2]; the chosen
route via triflate 27 allows for systematic variations at this
position.
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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