Total synthesis of (+)-batzelladine A and (-)-batzelladine D, and identification of their target protein.

Jun Shimokawa, Takanori Ishiwata, Koji Shirai, Hiroyuki Koshino, Aya Tanatani, Tadashi Nakata, Yuichi Hashimoto, Kazuo Nagasawa

Index: Chemistry 11(23) , 6878-88, (2005)

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Abstract

Asymmetric total synthesis of batzelladine A (1) and batzelladine D (2) has been achieved. Our synthesis of batzelladines features 1) stereoselective construction of the cyclic guanidine system by means of successive 1,3-dipolar cycloaddition reaction and subsequent cyclization, 2) direct esterification of the bicyclic carboxylic acid 35 with the guanidine alcohol 8 or 59 to construct the whole carbon skeleton of batzelladines, and 3) one-step formation of the alpha,beta-unsaturated aldehyde 53 from the primary alcohol 47 with tetra-n-propylammoniumperruthenate (TPAP), providing an efficient route to the left-hand bicyclic guanidine alcohol of batzelladine A (1). With the synthetic compounds 1 and 2 in hand, their target protein was examined by using immobilized CD4 and gp120 affinity gels. The results indicated that batzelladines A (1) and D (2) bind specifically to CD4.