Progress toward the total synthesis of maytansine. A stereoselective synthesis of the C-1 to C-7 moiety (northern zone)

✍ Scribed by A.I. Meyers; C.C. Shaw; Deane Horne; L.M. Trefonas; R.J. Majeste

• Publisher: Elsevier Science
• Year: 1975
• Tongue: French
• Weight: 174 KB
• Volume: 16
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)72249-0

✦ Synopsis

The complex structure of the potent anti-leukemic ansa macrolide, maytansine (3,' undoubtedly presents a formidable synthetic challenge.

We have recently reported2 the preparation of the cyclic carbinolamide gwhich represents the so-called "eastern zone" of maytansine.

In this communication we wish to describe a stereoselective synthesis of the "northern zone" 2 with all its attending stereochemistry corresponding to the contiguous carbon chain, C-l to C-7, of maytansine. 1, R = N-acetylalanine 1 Treatment of the aldehyde z2 with the cyclohexyllmine of proplonaldehyde (lithium diisopropylamide, -78". THF)$ followed by dehydration (oxalic acid -H20-THF, 25", 18h) afforded the unsaturated aldehyde 4 [70%. ir (film) 1690 cm-l; nmr (CDC13)d 9.77 (s, l), 6.40 (d, l)]. Further elaboration of 3 was accomplished by condensation using lithio methylacetate (-78'. -THF) and this furnished the B-hydroxy ester gas a mixture of diastereomers [74X, ir (film) 3450, 1745 cm"; nmr (CDC13) 6 5.33 (br.d, 1). 4.3-4.6 (m. 2). 3.73 (s, 3). 2.53 (br.d, 2). 1.70 (br.s, 3). 1.03 (br.d, 3)l. This mixture was transformed into the epoxide 5 (56%) using t-butyl