Nothapodytines A and B from Nothapodytes foetida

Cascade cyclization of 1-(2-yl-3-phenylprop-2-enyl)-6-oxo-1,6-dihydropyridine-2-carbonitrile radical: Mechanistic insights from DFT study

“…The cytotoxic quinoline alkaloid camptothecin, as well as its analogs mappicine and mappicine ketone (nothapodytine A and nothapodytine B), is of interest as antiviral and antitumor agents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. A wide variety of approaches to these alkaloids and their derivatives have been developed [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], which focused on constructing ring-fused molecular skeletons, as shown in Scheme 1.…”

A Modular Approach to Oxoindolizino Quinolines: Efficient Synthesis of Mappicine Ketone (Nothapodytine B)

“…[5] The requisite ketones B were viewed as products of benzylic-type oxidation of pyridones C, which would originate from various Claisen and Stille/Suzuki transformations of hydroxypyridones D. [6] Hydroxypyridones D are easily available through cycloaddition of the isomünchnone dipoles derived from diazo imides E. [7] We now illustrate the feasibility of this general strategy by way of an effective synthesis of mappicine ketone (1 a). Mappicine ketone, present in small amounts in Nothapodytes foetida (a plant found in India), [1] and formed by thermolysis of camptothecin, [8] displays strong, selective activity against herpes viruses (HSV-1 and HSV-2, including Acyclovirresistant forms) and human cytomegalovirus. [9,10] The synthesis of 1 a began with the formation of the known adduct 4 a by cycloaddition of the carbonyl ylide derived from 3 with methyl acrylate (Scheme 2).…”

“…Oxoindolizino quinolines include the natural products mappicine ketone (nothapodytine B, 1 a), [1] nothapodytine A (1 b), [1] mappicine (1 c), [2] and camptothecin (2 a), [3] as well as several chemotherapeutic derivatives of camptothecin, such as topotecan (2 b) and irinotecan (2 c). [3] While the importance of these and related alkaloids has already fostered many synthetic approaches, beginning with that by Stork and Schultz [4] some 30 years ago, additional, and in particular, efficient and flexible routes remain highly desirable for discovering derivatives with improved biological profiles.…”

Facile Syntheses of ABC Ring Skeleton of Camptothecin and Related Alkaloids

“…isolated recently from Nothapodytes foetida [2] (an oxidized derivative of Mappicine [3] and E-ring decarboxylated analogue of camptothecin) has been identified as an antiviral lead with reported selectivity against HSV-1, HSV-2, and HCMV. [4] Intense research on camptothecins has culminated in launching two successful compounds in clinical practice (irinotecan and topotecan) and several other compounds in clinical development.…”