Camptothecin 9-amino-

This method was effective for acylation of a hindered tertiary alcohol in the anticancer agent camptothecin by protected amino acids. 

Other Agents 9-Amino-Camptothecin, 9-Nitro-Camptothecin... 

Kirichenko AV, Rich TA, Newman RA, Travis EL. Potentiation of murine MCa-4 carcinoma radioresponse by 9-amino-20(S)-camptothecin. Cancer Res 1997 57(10) 1929-1933. 

Kirichenko AV, Mason K, Straume M, Teates CD, Rich TA. Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation. Int JRadiat Oncol Biol Phys 2000 47(4) 1043-1049. 

Pantazis P, Harris N, Mendoza J, Giovanella B. Conversion of 9-nitro-camptothecin to 9-amino-camptothecin by human blood cells in vitro. Eur J Haematol 1994 53(4) 246-248. 

Erickson-Miller, C.L., May, R.D., Tomaszewski, J., Osborn, B., Murphy, M.J., Page, J.G. and Parchment, R.E. (1997) Differential toxicity of camptothecin, otpotecan and 9-amino-camptothecin to human canine and murine myeloid progenitors (CFU-GM) in vitro. Cancer Chemotherapy and Pharmacology, 39, 467-474. 

Bastow KF, Wang HK, Cheng YC, Lee KH. Antitumor agents 59. 173. Synthesis and evaluation of camptothecin-4P-amino-4 -0-demethyl epipodophyllotoxin conjugates as inhibitors of mammalian DNA topoisomerases and as cytotoxic agents. Bioorg. 60. Med. Chem. 1997 5 1481-1488. 

Synthetic applications of AD which have already appeared and which are of potential industrial interest include the synthesis of propranolol (9) [48], diltiazem (10) [49], carnitine, and 4-amino-3-hydroxybutyric acid (11) [50], azole anti-fungals (12) [51], chloramphenicol (13) [52], reticuline intermediates (14) [53], camptothecin analogs (15) [54], khellactone (16) derivatives [55], taxol C-13 side chain (17) [56], halosarin [64], dehydro- xo-brevicomin [65], and antimalar-ial active cyclopenteno-l,2,4-trioxanes [57], as summarized in Figure 4. 

A practical six-step synthesis of (S)-camptothecin was developed by D.L. Comins and co-workers." In order to prepare the DE ring fragment, 2-methoxypyridine was Iithiated at C3 with mesityllithium and treated with A/-formyl-A/,A/, A/ -trimethyl ethylenediamine to form an -amino alkoxide in situ. In the same pot, the addition of n-BuLi brought about a directed lithiation at C4 to afford a dianion, which was trapped with iodine and treated with NaBHVCeCIs to give the desired 4-iodo-2-methoxy-3-hydroxymethyl pyridine in 46% yield. 

Marquis JF, Hardy I, Olivier M. Topoisomerase I amino acid substitutions, Glyl85Aig and Asp325Glu, confer camptothecin resistance in Leishmania donovani. Antimicrob Agents Chemother... 

Some novel hexacyclic and 7,9-disubstituted pentacyclic derivatives of camptothecin were synthesized by Terasawa et al. They were evaluated for in vitro cytotoxic activity against P388, HOC-21, and QG-56 and in vivo antileukemic activity against P388 in mice. Hexacyclics 213 and 215 have an additional 5-, 6-, or 7-membered ring cyclized at positions 7 and 9 of the camptothecin moiety. They were prepared by intramolecular cyclization of pentacyclic camptothecin derivatives of bicyclic amino ketone 212 or 214 and a tricyclic ketone 211, respectively (Scheme 46) (94JME3033). 

Analogs based on a novel template, ll-aza-(20S)-camptothecin 219, were obtained from a total synthesis and tested as potential anticancer drugs in the topoisomerase I enzyme cleavable complex assay. The parent ll-aza-(20S)-camptothecin 219 is derived by cyclization of the known aminopyridine derivative 3-(3-amino-4-picolylidene)-p-toluidine 217 and optically active tricyclic ketone 218 in 27% yield (Scheme 47) (95JMEn06). 

The topo I inhibitor camptothecin (16) is a natural alkaloid isolated from the Chinese tree Camptotheca acuminata it is used to treat gastric, rectal, colon, and bladder cancers. Several natural and synthetic derivatives including 9-amino 17) and 10-hydroxy (IS) camptote-cin, topotecan and irinotecan (20, CPT-ll) / potent antitumor and DNA... 

Other methods of esterification that do not utilize a carbodi-imide coupling method have also been explored. For example, the stereoselective esterification of 20-(S)-camptothecin, a hindered 3 ° alcohol, with amino acid derivatives was accomplished with the use of scandium triflate (Sc(OTf)3) in high yields while retaining the integrity of the amino acid stereocenter (eq 9). ... 

The importance of heterocycles in life was recognized as the nascent stage of organic chemistry two centuries ago with isolation of alkaloids such as morphine from poppy seeds, quinine from cinchona barks, and camptothecin from the Chinese joy tree. Today, heterocycles are found in numerous fields of biochemical and physiological such as photosynthesis, amino acids, DNA bases, vitamins, endogenous neurotransmitters, and so on. 

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