Dactomelyn

An unusual feature of dactomelyns is the presence of two halogen-substituted chiral centers. Since few methods are so far known for selective introduction of halogen atoms ai sp -hvbridi/ed carbon, the dactomelyns pose an extraordinary synthetic challenge. Another interesting feature of these natural products is the appearance of both chlorine and bromine atoms in the same molecule. One is struck, upon closer examination of the bicyclic pyran skeleton 1. by the fact that the chlorine atom is oriented toward the steri-cally less lavorable side of the molecule (the concave side), whereas the bromine atom is directed toward the convex side. 

In the synthesis presented here of Z-dactomelyn (1), three key radical steps permitted stereoselective construction of a bispyran skeleton with the development of halogen-substituted slereogenic centers. Starting from (-)-diethyl tartrate (2), the target compound was prepared in 26 steps with an overall yield of 0.04%. 

A collection of Laurencia elata from the coast of Victoria has provided the pyrano[3,2-7>]pyranyl vinyl acetylene elatenyne (666) (772), which is related to the known (Z)-dactomelyne (7). Japonenynes A (667), B (668), and C (669), which possess a furo[3,2-h]pyranyl framework, were isolated from Laurencia japonensis (773). Compound 669 may be an isolation (methanol) artifact although it is isolated as a single compound. The report of aplysiallene from the sea hare Aplysia kurodai (774) is erroneous and this compound is actually a known bromoallene (775) described earlier (7). The Vietnamese Laurencia pannosa contains pannosallene (670), which is closely related to the known laurallene... 

Examples of fused pyrans which can be obtained in a similar manner include 6-oxasteroids (95JCS(P1)1089) and bicyclic vinyl ethers (95CC1117), whilst a double radical cyclisation of 3-alkoxyacrylates features in a synthesis of 3Z-dactomelyne (95JA8017). 

During their synthesis of the Dactomelynes, Lee and co-workers employed sodium cyanoborohydride and titanium(IV) chloride95 to accomplish the regiose-lective cleavage of a benzylidene acetal [Scheme 3,57].%... 

Radical reactions have developed into indispensable methods in organic synthesis [1] and are often used as key steps in the construction of complex natural products. Impressive demonstrations are found in the following examples taken from the current literature the dactomelyne synthesis by Lee et al [2] the camptothecin synthesis by Curran et al., [3] and of (7)-deoxypancratistatin by Keck et al.,... 

The total synthesis of the marine natural product (5Z)-dactomelyne (1) requires the elaboration of the c -linked pyranopyran skeleton and the stereoselective introduction of halogen atoms on the tetrahydropyran rings. Lee et al. [2] solved this problem by using of )9-alkoxy-acrylates twice as radical acceptors (Scheme 1). 

Z)- and (3 )-Dactomelynes (905) and (906), isolated from the digestive glands of the sea hare Aplysia dactylomela, represent nonisoprenoid ethers characterized by a unique pyr-anopyranyl skeleton with ethyl and pentenynyl substituents. A characteristic feature of their structure is the chlorine substituent oriented on the sterically hindered side, whereas the bromine substituent avoids steric congestion. Construction of the pyranopyran skeleton via... 

Extracts of A. dactylomela are rich in other organic metabolites as has been demonstrated earlier. Gopichand et al, 552) isolated four new halogenated acetylenic ethers (864-867) from the digestive glands. These ethers which are fatty acid derived were two isomeric pairs named (3 )-12-epiobtusenyne (864), 12-677/-obtusenyne (865), (S )- and (3Z)-dactomelyne (866 and 867), respectively. Another isomeric pair, E)-and (Z)-ocellenyne (868 and 869), has been obtained from Aplysia oculifera (559). No biological activity has been described for any of these compounds. 

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