Total Synthesis of (−)-Amphidinolide K - ResearchGate

The lab reported that total synthesis of the natural product now requires only six steps from commercially available starting materials. Such a concise and efficient route is highly desirable for the synthesis of preclinical drug candidates and drugs.

Total Synthesis of (+)-Amphidinolide K - ResearchGate

 Va, P.; Roush, W. R.

Total Synthesis of (−)‐Amphidinolide K, Angewandte …

Jin, J.; Chen, Y.; Li, Y.; Wu, J.; Dai, W.-M. "Total Synthesis of Amphidinolide Y by Formation of Trisubstituted (E)-Double Bond via Ring-Closing Metathesis of Densely Functionalized Alkenes." 2007, 2585-2588.

Total Synthesis of iso-Epoxy-Amphidinolide N by …

Fürstner,, A.; Bouchez, L. C; Funel, J.-A.; Liepins, V.; Poree, F.-H.; Gilmour, R.; Beaufils, F.; Laurich, D.; Tamiya, M. "Total syntheses of amphidinolide H and G." 2007, 9265-70.

Ghosh, A. K.; Gong, G. "Total Synthesis and Structural Revision of (+)-Amphidinolide W,"

Toward a total synthesis of amphidinolide N: …

Total syntheses of 1 and 3–5 have been reported to date. Amphidinolide T4 was synthesized in 2002 by Fürstner and coworkers by taking advantage of an efficient ring-closing metathesis to form the macrocycle. Related strategies were applied by the same group to the syntheses of T1, T3, and T5 reported in 2003. Amphidinolide T1 was first synthesized by Ghosh and Liu in 2003, utilizing a macrolactonization reaction to form the 19-membered ring.

Total Synthesis and Structural Revision of (+)‐Amphidinolide W

The foundation of our strategy for the synthesis of both amphidinolide T frameworks (the hydroxy ketone array found in 1 and its reversed positioning in 2–5) is the use of nickel-catalyzed reductive coupling reactions of alkynes, the aforementioned intramolecular alkyne-aldehyde coupling reaction, as well as an intermolecular reductive coupling of an alkyne and epoxide. As shown in , the product of the former, an allylic alcohol, would serve as a latent α-hydroxy ketone moiety.

Ghosh, A. K.; Liu, C. "First total synthesis of (+)-amphidinolide T1,"   2004,  255-302.�

An enantioselective first total syntheis of amphidinolide W (2) ..

Completion of the total synthesis of 1 indicated that our strategy of reductive macrocyclization was indeed a viable route to amphidinolide T1. Nevertheless, a critical issue in using this strategy for the synthesis of other members (T2–5) was the reversed hydroxy ketone pattern at C12 and C13 (see ). In our next synthetic undertaking, we set out to address this issue by studying the reductive cyclization of alkynal 9, and whether it would exert a high degree of substrate diastereocontrol in a cyclization using an achiral catalyst system as it contains β-branching with respect to the aldehyde instead of α-branching ().

Lepage, O.; Kattnig, E.; Fürstner, A. "Total Synthesis of Amphidinolide X,"

Total Syntheses of Amphidinolide H and G - …

Our interest in the amphidinolide T natural products stemmed from the presence of the α-hydroxy ketone and homoallylic ester moieties, both of which are patterns of functional groups that we have prepared using nickel-catalyzed, alkyne-electrophile reductive coupling reactions developed in our laboratory.,, Our synthetic strategy represents a novel approach to the T natural products, based on an alternate ring-closing method (). In contrast to all previously reported syntheses of amphidinolide natural products (i.e. T1 or otherwise), this approach features the installation of a stereogenic center (>10:1 diastereoselectivity) during the macrocyclization event. Herein, we disclose the implementation of this strategy in a full account of our synthesis of amphidinolide T1 and a previously unreported synthesis of T4.

Williams, D. R.; Meyer, K. G. "Total Synthesis of (+)-Amphidinolide K,"   2001, 765-766�.

ChemInform Abstract: Total Synthesis of (‐)‐Amphidinolide K.

Although the positions of the alkyne and aldehyde portion of the corresponding alkynal cyclization substrates 8 and 9 are inverted relative to one another, earlier synthetic intermediates nevertheless share many structural and stereochemical features (). The synthesis of amphidinolide T1 would necessitate alkynyl acid 10 and homoallylic alcohol 11, while amphidinolide T4 requires alkenyl acid 12 and hydroxyenyne 13.