Simplification of antitumoral phenanthroindolizidine alkaloids: Short synthesis of cytotoxic indolizidinone and pyrrolidine analogs

Design, Synthesis, and Biological Activity of Sulfonamide Analogues of Antofine and Cryptopleurine as Potent and Orally Active Antitumor Agents

“…The crude product was separated by silica gel column chromatography (CH 2 Cl 2 /EtOAc, 10:1) to give 10b ( 151.4, 150.2, 144.7, 139.0, 132.8, 129.8, 128.9, 127.0, 123.9, 120.6, 119.3, 117.7, 104.5, 103.3, 56.3, 56.0, 52.1, 42.5, 33.2, 32.9, 24.5, 22.7; IR (CHCl 3 ) υ max 2938, 1636, 1517, 1416, 1338, 32 1255, 1207, 1032, 840, 749 (cm -1 (R)-N-(2, 11,12,13,13a,h]pyrrolo [1,2b]isoquinolin-6-yl)methanesulfonamide (12a 1, 150.6, 149.9, 134.8, 134.5, 130.4, 129.6, 126.5, 126.3, 124.3, 123.2, 119.9, 113.2, 104.8, 103.8, 56.04, 55.96, 55.2, 45.4, 39.3, 33.8, 32.7, 23.6; IR (CHCl 3 ) υ max 3015, 2942, 1601, 1512, 1465, 1317, 1258, 1203, 1149, 1031, 980, 841, 747 (cm -1 (R)-N-(2, 12,13,14,14a,h]pyrido [1,2b]isoquinolin-6-yl)methanesulfonamide (12b). This compound was prepared from 10b ( 9, 150.8, 149.9, 134.8, 134.3, 130.6, 130.2, 126.8, 126.7, 124.0, 120.9, 119.8, 113.3, 104.6, 103.8, 56.1, 56.0, 52.6, 42.6, 39.3, 33.0, 32.9, 24.6, 22.9; IR (CHCl 3 ) υ max 3259, 2936, 1734, 1615, 1513, 1469, 1418, 1256, 1153, 1036, 969, 844, 753 (cm -1 (R)-N-(2, 11,12,13,13a,h]pyrrolo [1,2-b] 34 148.6, 133.6, 129.5, 128.0, 127.0, 126.7, 126.0, 124.0, 123.5, 120.5, 116.0, 103.8, 103.5, 60.3, 55.9, 55.8, 54.9, 53.6, 39.5, 33.7, 31.2, 21.6; IR (CHCl 3 ) υ max 3015, 2942, 2831, 1601, 1512, 1317, 1258, 1203, 1149, 1031, 980, 841, 747 (cm -1 (R)-N-(2, 12,13,14,14a,h]pyrido [1,2...…”

“…10 Intensive structure-activity-relationship (SAR) studies revealed several essential structural elements that are required for the cytotoxic activity of antofine and its related phenanthroindolizidine alkaloids. 3,6,11 For example, the nonbonding electron pair on the nitrogen atom is important for significant activity. The pentacyclic system is also crucial for high cytotoxic activity.…”

Effect of conformational rigidity on the stereoselectivity of nucleophilic additions to five-membered ring bicyclic oxocarbenium ion intermediates

“…We have developed a model that accounts for electronic, steric, and torsional effects on these transformations 11,12 . The conclusions of these studies can be used in a number of settings, including reactions of oxocarbenium ions with carbon and hydride nucleophiles 17 and nucleophilic additions to cyclic iminium ions 18,19 . The stereochemical model can be applied to the chemistry of carbohydrates 20 and nucleosides, 21 which required consideration of the influence of fused rings, which also control the reactions of six-membered-ring acetals 22,23 .…”

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…[42] Reaction of the proline derivative 32 with trimethyl[(1phenylethenyl)oxy]silane in the presence of (diacetoxyiodo)benzene and molecular iodine, which resulted in the formation of a ketone 33 (Scheme 7,b). [43,44] A convenient method for the synthesis of 1,3diketone 36 containing a pyrrolidine fragment is the reaction of 2-ethoxypyrrolidine 34 with dibenzoylmethane (35) in the presence of a mixture of gold chloride and silver triflate in acetonitrile at room temperature (Scheme 8,a). [45,46] Bhat and coworkers [47] have synthesized the 1phenyl-2-(pyrrolidin-2-yl)ethan-1-one 39 by the interaction of Meldrum's benzoyl 38 with 2-hydroxypyrrolidine 37 in the presence of N,N'-dimethylethylenediamine (DMEDA), Meldrum's acid was isolated as by-product (Scheme 8,b).…”