Synthesis of (-)-4-aza-4-deoxypodophyllotoxin from (-)-podophyllotoxin

Tetrahedron Letters

Volumn 40, Issue 51, 1999, Pages 9107-9110

  Hitotsuyanagi, Yukio ^a   Kobayashi, Masatsugu ^a   Morita, Hiroyuki ^a   Itokawa, Hideji ^a   Takeya, Koichi ^a  

^a TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCES   (Japan)

Author keywords

4 Aza 4 deoxypodophyllotoxin; Curtius rearrangement; Cytotoxicity; Podophyllotoxin

Indexed keywords

4 AZA 4 DEOXYPODOPHYLLOTOXIN; PODOPHYLLOTOXIN; UNCLASSIFIED DRUG;

ALKYLATION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; CYTOTOXICITY; DRUG SYNTHESIS; IN VIVO STUDY; LEUKEMIA P 388; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0033579609     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01932-2     Document Type: Article

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10. All attempts to improve the selectivity of this reduction were unsuccessful due to ready migration and/or reductive elimination of the protective ethoxycarbonyl groups.
11. The stereochemistry of diols and was determined by chemical evidence. Diol was subjected to hydrogenolysis, and successive dehydration under Mitsunobu conditions, which proceeds through an anti E2 mechanism, gave Z-olefin In the same manner, E-olefin was obtained from diol (equations presented) Iimori, T.; Ohtsuka, Y; Oishi, T. Tetrahedron Lett. 1991, 32, 1209-1212.
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17. 5N, ref: 135.5 ppm) δ 173.43 (s), 153.35 (s), 148.20 (s), 141.43 (s), 141.26 (s), 138.71 (s), 137.99 (s), 115.24 (s), 110.84 (d), 109.06 (d), 101.34 (t), 98.27 (d), 71.21 (t), 60.49 (q), 56.10 (q), 49.13 (d), 47.76 (d), 42.84 (d).
18. Although one of the referees urged us to add the results of the in vivo biological evaluation of analogue 4 to enhance the value of this manuscript, we decided to disclose the salient points of our study at this stage since the preparation of a sufficient amount of the analogue and such in vivo biological evaluation would involve an extended period of time, inevitably delaying the urgent publication of this synthetic work.