Arisugacin, synthesis

Other procedures using TPAP/NMO/PMS/CH Cl include steps in the synthesis of (+)-altholactone (lactol to lactone) [78] antheliolide A [168] the AChE inhibitor (+)-arisugacin A and B (primary alcohol to aldehyde step also) [83] the marine macrolide amphidinolide T1 [169] the alkaloid (+)-batzelladine D cf. mech. 

It is noteworthy that stereochemical control of the two new stereogenic centers at C4a and Cl2b ultimately stems from the stereochemistry at Cl through the intramolecular Diels-Alder reaction. Hence, an optically pure 46 should lead to an enantioselective preparation of a-epoxy lactone 48, thereby ultimately leading to an enantioselective synthesis of arisugacin A [1], LAH reduction of ( )-a-epoxy lactone 48 led to epoxy diol 49 in 78%... 

To achieve synthesis of (-)-arisugacin A [1], (7 J-89 was obtained readily from 2-methyl-l,3-cyclohexanedione 88 in 4 steps with an overall yield of 46%, featuring vinylogous ester formation, Stork-Danheiser double alpha methylation,52,68,69 vinyl Grignard addition followed by acidic work-up,68 and an asymmetric CBS reduction [Scheme 21].70,71... 

The retrosynthetic analysis of arisugacin is shown in Scheme 12.2. It is clear to us that this formal [3+3] cycloaddition method could be invaluable to achieve a practical total synthesis of arisugacin A 6 or other family members and their analogs [20]. Specifically, the reaction of a,(3-unsaturated iminium salts 13 with 6-aryl-4-hydroxy-2-pyrones 14 should provide a facile access to the advanced pentacyclic intermediate 12. 

Although the proposed route for the synthesis of arisugacin A (Scheme 12.10) can be feasible based on our development of the key formal [3+3] cycloaddition step (13 + 14 12) [23,24], there are two major uncertainties that could have rendered this effort futile. First, sterically congested a,(3-unsaturated iminium salts such as 13 can impede the formal [3+3] cycloaddition, although the work... 

To achieve a total synthesis of (-)-arisugacin A 6, R-83 was obtained readily from 2-methyl-1,3-cyclohexanedione... 

Also see Hsung, R. P. Cole, K. P. (2004) The total synthesis of (—)-arisugacin A. In Harmata, M. (Ed.) Strategies and Tactics in Organic Synthesis, Vol. 4, Elsevier Science, Pergamon Press Oxford, England, pp. 41-70. 

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