Novel 29-nor-3,4-seco-cycloartane triterpene methyl esters from the aerial parts of Antirhea acutata Dongho Lee, a Muriel Cuendet, a Franklin Axelrod, b Pedro I. Chavez, c Harry H. S. Fong, a John M. Pezzuto a and A. Douglas Kinghorn a,p a Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA b Department of Biology, University of Puerto Rico-Rõ Âo Piedras, San Juan, PR 00931, USA c College of Pharmacy, Glendale Campus, Midwestern University, Glendale, AZ 85308, USA Received 17 May 2001; accepted 20 June 2001 Abstract ÐFour novel 29-nor-3,4-seco-cycloartanes, 6S)-hydroxy-25-methoxy-29-nor-3,4-seco-cycloart-430),23-dien-3-oic acid methyl ester 1), 6S,25)-dihydroxy-29-nor-3,4-seco-cycloart-430),23-dien-3-oic acid methyl ester 2), 6S)-hydroxy-24-oxo-29-nor-3,4-seco- cycloart-430),25-dien-3-oic acid methyl ester 3), and 6S)-hydroxy-24j )-hydroperoxy-29-nor-3,4-seco-cycloart-430),25-dien-3-oic acid methyl ester 4), along with a semi-synthetic acetylated derivative, 6S,24j )-diacetyloxy-29-nor-3,4-seco-cycloart-430),25-dien-3- oic acid methyl ester 5), were isolated and characterized from the aerial parts of Antirhea acutata DC.) Urb. Rubiaceae). Their structures and absolute stereochemistry were elucidated by spectroscopic and chemical methods. Compounds 1 ± 5 are based on the unprecedented 29-nor-3,4-seco-cycloartane skeleton. Compound 4 showed moderate inhibitory activities in cyclooxygenase-1 and -2 assays IC 50 45.7 and 18.4 mM, respectively), while the other four isolates were inactive. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Members of the genus Antirhea Rubiaceae) are shrubs or trees and represent about 40 species that grow in the West Indies, Central America, and East Asia. 1 The whole plant of A. borbonica is used in folk medicine for the treatment of cholera, diarrhea, hemorrhage, and stomach ulcers. 2 Several indole alkaloids have been reported from A. lucida, 3 A. protoricensis, 4 and A. putaminosa. 5 In our search for naturally occurring cancer chemopreventive agents, the aerial parts of Antirhea acutata DC.) Urb. 6 were selected for detailed investigation, since its ethyl acetate-soluble extract showed signi®cant activities in a cyclooxygenase-1 COX-1) inhibition assay 100% inhibition at 70 mg/mL) and in a 1,1-diphenyl-2-picrylhydrazyl free-radical anti- oxidant assay IC 50 34.7 mg/mL). Agents which inhibit the carcinogenic process subsequent to initiation, including estrogen analogues and COX inhibitors, and antioxidants that scavenge free radicals, are considered as carcinogen- suppressing and carcinogen-blocking agents, respec- tively. 7,8 In a preliminary communication, we have reported an initial phytochemical and biological investigation on this plant, with the isolation of a new COX-inhibitory 29-nor- 3,4-seco-cycloartane 6), as well as a new antioxidant phenylpropanoid-epicatechin, and a new cycloartane derivative, which was not active in any of the bioassays used. 9 We currently report the isolation of ®ve further novel 29-nor-3,4-seco-cycloartane derivatives 1±5) from A. acutata, in addition to their absolute stereochemistry and biological evaluation. Prior to our work with A. acutata, there have been no reports on either the biological activity or phytochemistry of this plant. Tetrahedron 57 2001) 7107±7112 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-402001)00664-0 Keywords: Antirhea acutata; Rubiaceae; 29-nor-3,4-seco-cycloartane; cyclooxygenase-1 and -2. p Corresponding author. Tel.: 11-312-996-0914; fax: 11-312-996-7107; e-mail: kinghorn@uic.edu