Seco-analogues

It is very important to clarify the minimum structural requirements for paclitaxel and taxoids to exhibit anticancer activity by looking at simplified structure analogues. Along this line, we have investigated the role of the A ring by synthesizing novel nor-seco analogues of paclitaxel and docetaxel.37,96... 

Upon inspection of the NMR spectra of seco analogues 166,167, and 169, temperature-dependent behavior was observed for 166 and 167. By contrast, gem-dimethyl analogue 169 had a sharply resolved H NMR spectrum at room temperature. 

Another class of analogues which we felt would be of interest were the ring-D seco analogues of artemisinin (viz. 180), derived conceptually from scission of the 8a, 9 bond of 1 (Eq. 22). 

Finally, facile reduction of aldehyde 10 to alcohol 227 occurred with NaBH4 in MeOH at 0 °C. Exposure of 227 to acid in CH2C12 led to the expected tmns-ketali-zation product 182 in 79% overall yield. Seco-analogue 182 has, of course, the A, B, and C rings of artemisinin. 

Table 7. In Vitro Antimalarial Activities of Seco Analogues of Artemisinin...

A seven-step sequence of reactions has been described for the conversion of oestradiol methyl ether into its 9,11-seco-analogue,111 as follows oestradiol methyl... 

In addition to benzylisoquinolines, the family Lauraceae furnishes phenanthro-quinolizidine alkaloids such as the previously mentioned cryptopleurine (31) [77], a highly cytotoxic and vesicant substance first isolated from Cryptocarya pleurosperma [78]. These alkaloids are closely related structurally to the phenanthroindolizidines, a group of bases found in the families Asclepidaceae and Moraceae that are likewise vesicant. An example is tylocrebrine (56), which is elaborated by a Queensland plant from each family, Tylophora crebriflora [79] and Ficus septica [80], respectively. In the latter it occurs along with the seco analogue septicine (57), its presumed biosynthetic precursor. Apart from phenanthroindolizidines, certain Ficus spp. produce some simple pyrrolidine bases such as ficine (58) that are noteworthy because of their flavonoid substituents [81],... 

Ferrier carbocyclization of 38 (also prepared from D-glucose) has been utilized in the synthesis of 39 and 40 (Scheme 7), molecules which can be viewed as seco analogues of the Amaryllidaceae alkaloids, lycorocidine and narciclasine. ... 

Sanchra JD, Ramos MT, Avendano C. Synthesis of 5-iV-acety-lardeemin seco-analogues. Tetrahedron 1998 54(5-6) %9 80. 

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