Reference

Synthesis and in vitro biological evaluation of b,g-methano analogs of methotrexate and aminopterin

Synthesis and in vitro biological evaluation of b,g-methano analogs of methotrexate and aminopterin. 41. Rosowsky, Andre; Forsch, Ronald A.; Moran, Richard G.; Freisheim, James H. (Dana-Farber Cancer Inst., Harvard Med. Sch., Boston, MA 02115, USA). Pteridines, 2(3), 133-9 (English) 1991.There are some reagents with their cas registry numbers 54-62-6 and 1117-71-1 are used in this study. CODEN: PTRDEO. ISSN: 0933-4807. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) b,g-Methano derivs. of methotrexate (MTX) and aminopterin (AMT) were synthesized with the aim of assessing the effect of this side-chain modification on dihydrofolate reductase (DHFR) inhibition, folylpolyglutamate synthetase (FPGS) inhibition, and tumor cell growth inhibition. Mixed carboxylic-carbonic anhydride (MCA) coupling of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) and di-Me trans-a-(2-carboxycyclopropyl)glycinate, followed by alk. hydrolysis, afforded N-(4-deoxy-N10-methylpteroyl)-a-(trans-2-carboxycyclopropyl)glycine (b,g-methanoMTX) as a mixt. of the four possible diastereomers with trans substitution on the cyclopropane ring. N-(4-Amino-4-deoxypteroyl)-trans-a-(2-carboxycyclopropyl)glycine (b,g-methanoAMT), also as a diastereomer mixt., was obtained from 4-amino-4-deoxy-N10-formylpteroic acid (fAPA) and di-Me trans-a-(2-carboxycyclopropyl)-glycinate by MCA coupling and alk. hydrolysis of the ester and N10-formyl groups. b,g-MethanoMTX and b,g-methanoAMT may be viewed as MTX and AMT analogs with a conformationally restricted side chain. In vitro biol. activity data for these novel compds. support the view that the active site of DHFR, already known for its ability to tolerate modification of the g-carboxyl group of MTX and AMT, can likewise accommodate substitution on the b- and g-carbons. .

Chemoselective ring construction from unsymmetrical 1,6-dienes via radical addition of sulfonyl halides

Chemoselective ring construction from unsymmetrical 1,6-dienes via radical addition of sulfonyl halides. De Riggi, I.; Gastaldi, S.; Surzur, J. There are some commonly used reagents like 1117-71-1 in this article. M.; Bertrand, M. P.; Virgili, Albert (Lab. Chim. Org. B, Fac. Sci. Saint-Jerome, Marseille 13397, Fr.). J. Org. Chem., 57(23), 6118-25 (English) 1992. CODEN: JOCEAH. ISSN: 0022-3263. DOCUMENT TYPE: Journal CA Section: 21 (General Organic Chemistry) The sulfonyl radical-promoted cyclizations of 1,6-unsym. dienes can be totally chemoselective. The addn. of tosyl halides to various 1,6-dienes bearing both a nucleophilic and an electrophilic double bond clearly indicates that this attractive property is not related to the generally accepted electrophilic nature of tosyl radical. Thus, addn. of tosyl bromide to N,N-diallylacrylamide affords N-allyl-4-(bromomethyl)-3-(tosylmethyl)-2-pyrrolidinone. The chemoselectivity is likely to originate from the reversibility of the first step, i.e., tosyl radical addn. to the double bond, which favors the formation of the adducts resulting from the intermediate radical that cyclizes faster. .