Sarcophytol synthesis

The Stork-Takahashi method has been applied to the synthesis of a number of macrocyclic natural products including Muscone,217 Sarcophytol-A2H and Peri-planone B.220... 

The first total synthesis of sarcophytol A (3), which was reported by Takayanagi et al. in 1990, ° was achieved in a highly stereo- and enantioselective manner starting from , -famesol (91) it included (1) a newly developed Z-selective (Z > 35 1) Horner-Emmons reaction with a phosphonate nitrile, (2) modified cyanohydrin macrocyclization, and (3) enantioselective (93% ee) reduction of macrocyclic ketone 100 as its key steps (Scheme 6-1). 

Then Li et al. reported on a concise total synthesis of ( )-sarcophytol A (3) from the derivative of , -farnesol (91) by a low-valent titanium-mediated intramolecular McMurry olefination strategy (Scheme 6-4). ... 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

The closure of the macrocyclic ring by means of an intramolecular 8 2 reaction is a straightforward approach, and sulfur-stabilized carbanion alkylation has been successfully applied in the synthesis of 14-membered cembranoids. The synthesis of nephthenol (40) and cembrene A (59) is an example of this methodology. In Li and Yue s report, the total synthesis of ( )-sarcophytol M (17) was achieved from ger-aniol (137) through 12 steps and in 8.9% overall yield with an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as a key step. This example is the first of the closure of a macrocyclic ring with the intramolecular nucleophihc addition of a sulfur-stabilized carbanion to a ketone (Scheme 6-7). 

Characteristic to some important cembrane diterpenoids, such as isocembrene, cembrene, cembrene C, and sarcophytol A, is a 1,3-diene unit in the macrocyclic skeleton. In continuation of our ongoing project on the total synthesis of cembrane-type diterpenoids, we intended to explore a novel macrocyclization method to... 

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

Sarcophytol B. McMurry has utilized a diastereoselective pinacol cyclization of a 1,14-dialdehyde in the final step of a five-step synthesis of sarcophytol B, a cem-brane sesquiterpene (Eq. 3.8) [25]. This work established the relative stereochemistry of the natural product [26]. 

Takayanagi, H., Sugiyama, S., and Morinaka, Y., A ketal Claisen rearrangement for a-ketol isoprene unit elongation. Application to a practical synthesis of sarcophytol A intermediate, J. Chem. Soc., Perkin Trans. 1, 751, 1995. 

Takayanagi, H., Kitano, Y, and Morinaka, Y. (1994) Total synthesis of sarcophytol A, an anticarcinogenic marine cembranoid. /. Org. Chem, 59,2700-2706. 

Takashi, T, Yokoyama, H., Haino, T, and Yamada, H. (1992) Enolate reactions on macrocydic ring systems total synthesis of ( )-sarcophytol A./. Org. Chem., 57, 3521-3523. 

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