Studies in polyphenol chemistry and bioactivity. 1. Preparation of building blocks from (+)-catechin. Procyanidin formation. Synthesis of the cancer cell growth inhibitor, 3-O-galloyl-(2R,3R)-epicatechin-4β,8-[3-O- galloyl-(2R,3R)-epicatechin]

Journal of the American Chemical Society

Volumn 121, Issue 51, 1999, Pages 12073-12081

  Tückmantel, Werner ^a   Kozikowski, Alan P ^a   Romanczyk Jr , Leo J ^b  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b MARS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL DERIVATIVE; ANTINEOPLASTIC AGENT; BORANE DERIVATIVE; CATECHIN; EPICATECHIN; EPIGALLOCATECHIN GALLATE; ETHYLENE GLYCOL; KETONE DERIVATIVE; NATURAL PRODUCT; OLIGOMER; POLYPHENOL; PROANTHOCYANIDIN; PROCYANIDIN; PROTEIN KINASE C INHIBITOR;

ACYLATION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CACAO; CANCER INHIBITION; CHEMICAL REACTION; DRUG ACTIVITY; DRUG SYNTHESIS; ENANTIOMER; ENZYME INHIBITION; OXIDATION; STEREOCHEMISTRY;

EID: 0037538675     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja993020d     Document Type: Article

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174. 2, but the reaction works fine anyway.
175. HPLC separation of the column forerun resulted in isolation or enrichment of residual starting material and of byproducts to which the following structures have tentatively been assigned: the 2-alkoxy derivative; a product containing two epicatechin moieties linked by an ethylenedioxy group, most likely both in their 4-positions; and a product of 2-fold oxidation in positions 2,4 or 4,4 which are spanned by a single ethylenedioxy group.
176. - form) but remained dissatisfied because of the large amount of resin needed. Eventually, it was found that a slight excess of 4-(dimethylamino)pyridine (DMAP) serves well for this purpose. The formation of solid, dark-colored molecular complexes between DDQ and the three isomeric aminopyridines has been reported: Tosi, G.; Bruni, P.; Cardellini, L. Gazz. Chim. Ital. 1984, 114, 125.
177. According to ref 1t (p 92), only a single compound, a natural product, with 2,3-cis-3,4-cis stereochemistry is known.
178. For a characteristic example, see: Kolodziej, H. Phytochemistry 1986, 25, 1209.
179. Reliance on circular dichroism as a source of errors is documented in: Hundt, A. F.; Burger, J. F. W.; Steynberg, J. P.; Steenkamp, J. A.; Ferreira, D. Tetrahedron Lett. 1990, 31, 5073.
180. Balas, L.; Vercauteren, J.; Laguerre, M. Magn. Reson. Chem. 1995, 33, 85.
181. A variety of esters and urethanes, as well as two monobromides, the 3,3-dideoxy derivative, and the diketone, have been investigated by us. One group of researchers reported crystallization of the peracetate (ref 34a) but others described the compound as amorphous (ref 84).
182. The free dimeric proanthocyanidin, fisetinidol-4,8-catechin (fisetinidol is the 5-deoxy analogue of catechin), has been crystallized, but an X-ray diffraction analysis failed to yield its structure as a consequence of conformational disorder: unpublished work quoted by R. W. Hemingway in Polyphenols 96 (proceedings of the conference in Bordeaux, France, July 15-18, 1996); Vercauteren, J.; Chèze, C.; Triaud, J., Eds.; Editions INRA, Paris, 1998: pp 81-103.
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184. A summary of the truly bewildering sole reliance, until quite recently, on questionable empirical techniques for regiochemical assignment is given in: Balas, L.; Vercauteren, J. Magn. Reson. Chem. 1994, 32, 386.
185. (a) Kiehlmann, E.; Tracey, A. S. Can. J. Chem. 1986, 64, 1998.
186. (b) Kiehlmann, E.; Lehto, N.; Cherniwchan, D. Can. J. Chem. 1988, 66, 2431.
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198. (a) Langhammer, L.; Rauwald, H.-W.; Schulze, G. Arch. Pharm. (Weinheim) 1981, 114, 424.
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212. Romanczyk, L. J., Jr.; Kozikowski, A. P.; Tueckmantel, W.; Lippman, M. E. PCT Int. Appl. WO 99/19,319, April 22, 1999. Briefly, the observed cell growth (as percent of the growth of untreated cells) at concentrations of 24 of 50 and 100 mg/L is 84 and 62% for MDA MB 231 cells, 33 and 8% for MDA MB 435 cells, 23 and 2% for MDA 231 cells, and 55 and 7% for MCF-7 cells, respectively.