Minfiensine

This chapter is based on an approach by Overman and coworkers who completed the first enantioselective total synthesis of (+)-minfiensine (1) in 2005. ... 

Upon addition of excess trifluoroacetic acid to the crude Heck product, an iminium ion cyclization furnishes the tetracyclic core of minfiensine (1) without cleavage of the Boc group. 

Reduction of the a,p-unsaturated ester 21 with LiAlH4 and subsequent removal of the carbamate protection group provides minfiensine (1) in 85 % yield over two steps. 

In this chapter, a concise catalytic asymmetric synthesis entry to alkaloids containing the l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9F/-carbazole (4) ring is presented and the enantioselective total synthesis of minfiensine (1) is discussed in detail. 

Minfiensine (99) [43] exemplifies a variety of indole alkaloids containing the novel l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9/7-carbazole ring skeleton. These include minfiensine (99), vincorine (100) [44], corymine (101) [45], and echitamine (102) [46] (Fig. 4). They exhibit a number of impressive biological activities, including significant anticancer activity [47]. Since the first characterization of the first akuammiline alkaloid member echitamine (102), more than 80 years ago, only a few successful syntheses of this challenging tetracyclic system have been reported. 

Minfiensine (99) was first synthesized by Overman and coworkers in 2005 [48] (Scheme 19). Their synthesis commenced with acid-catalyzed transamination of... 

Scheme 19 Total synthesis of minfiensine (99) by Overman and coworkers...

Massiot G, Thepenier P, Jacquier MJ, Men-Olivier LL, Delaude C (1989) Normavacurine and minfiensine, two new alkaloids with C19H22N2O formula from Strychnos species. Heterocycles 29 1435-1438... 

Shen L, Zhang M, Wu Y, Qin Y (2008) Efficient assembly of an indole alkaloid skeleton by cyclopropanation concise total synthesis of ( )-minfiensine. Angew Chem Int Ed 47 3618-3621... 

Dounay AB, Overman LE, Wrobleski AD (2005) Sequential catalytic asymmetric Heck-iminium ion cyclization enantioselective total synthesis of the Strychnos alkaloid minfiensine. J Am Chem Soc 127 10186-10187... 

In 2005, the Overman group reported the first total synthesis of minfiensine... 

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