Microtubule stabilizing agents laulimalide

Paterson, I., De Savi, C., Tudge, M. Total Synthesis of the Microtubule-Stabilizing Agent (-)-Laulimalide. Org. Lett. 2001,3, 3149-3152. 

Paterson I, De Savi C, Tudge M. Total synthesis of the microtubule-stabilizing agent (—)-laulimalide. Organic Lett. 2001 3 (20) 3149-3152. 

Chart 9 Schematic representation of the principal microtubule stabilizing agents (MSAA) paclitaxel (10) and docetaxel (11), epothilones A-D (12-15), discodermolide (16), eleutherobin (17) and sarcodictyin (18), laulimalide (19) and peloruside A (20)... 

A small, but structurally diverse collection of naturally occurring non-taxane microtubule stabilizing agents (MTS) has been discovered over the last decade. These include the epothilones (EPO), eleutherobin, laulimalide, dicytostatin (Figure 2) and (+)-discodermolide. 

Mooberry, S.L., Tien, G., Hernandez, A.H., Plubrukarn, A., and Davidson, B.S. (1999) Laulimalide and isolaulimahde, new paditaxel-like microtubule-stabilizing agents. Cancer Res., 59, 653-660. 

In the laboratory of J. Mulzer, the total synthesis of laulimalide, a microtubule stabilizing antitumor agent, was accomplished. The C9 stereochemistry of the natural product was introduced using the Jacobsen HKR on a diastereomeric mixture of a terminal epoxide. The epoxide mixture was prepared via the Corey-Chaykovsky epoxidation of citronellal. The HKR proceeded in high yield and high selectivity at room temperature, and the products were easily separated by flash chromatography. The did was converted into the diastereomerically pure epoxide in three steps. 

Ahmed, A., Hoegenauer, E. K., Enev, V. S., Hanbauer, M., Kaehlig, H., Oehler, E., Mulzer, J. Total Synthesis of the Microtubule Stabilizing Antitumor Agent Laulimalide and Some Nonnatural Analogues The Power of Sharpless Asymmetric Epoxidation. J. Org. Chem. 2003, 68, 3026-3042. 

The novel marine natural product laulimalide (65), a metabolite of various sponges, has received attention as a potential antitumor agent due to its taxol-like ability to stabilize microtubules. There has been considerable synthetic effort toward 65, culminating within not more than 2 years in as many as ten... 

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