Organic Chemistry: Current Research
Open Access
ISSN: 2161-0401
+44 1478 350008
ISSN: 2161-0401
+44 1478 350008
Faiza Diaba, Sergi Jansana and Josep Bonjoch
Barcelona University, Spain
Scientific Tracks Abstracts: Organic Chem Curr Res
Daphniphyllum alkaloids, isolated from the Daphniphyllum genus, are a large family of natural compounds containing over than 320 members with more than 20 different polycyclic frameworks. Besides their fascinating structures, many of these compounds have showed a wide range of biological activities naming anticancer, anti- HIV, antioxidant, antiviral, vasorelaxation and nerve growth factor-regulation. Daphenylline, isolated in 2009 from the fruit of D. longeracemosum by Hao and co-workers, is the first member of the Daphniphyllum alkaloids including a benzene ring in the core structure.3 Since its isolation, four total syntheses of daphenylline4 and three other approximations to either the ABCE or the ACDE tetracyclic structures5 were reported. In this investigation we achieved the synthesis of the ACDEF pentacyclic structure of daphenylline from 1-methyl-2-tetralone as a starting material. The synthesis started with the preparation of enamide 1 which underwent a 5-endo-trig radical cyclization in the presence of Bu3SnH and AIBN6 to provide indol 2 with all-carbon quaternary centers present in Daphenylline. Next, a stereocontrolled allylation followed by a diastereoselective reduction of the resulting enamide with NaBH3CN and acetic acid gave 3 embedding the cis-hydroindole structure. Alkene 3 was converted to the corresponding acid using a two steps sequence: i) hydroboration-oxidation, ii) oxidation in the presence of TEMPO and NaClO. The acid was treated with SOCl2 and then submitted to the classical Friedel-Crafts conditions to provide the seven-membered ring in 4 with an excellent yield. After a 1,2-carbonyl transposition of ketone 4 using a four steps sequence, alkylation provided ester 5 with the correct stereochemistry which after a second friedel Crafts cyclization gave 6 with the ACDEF pentacyclic core of daphenylline.
Recent Publications
1. Chattopadhyay A K, Hanessian S (2017) Recent progress in the chemistry of Daphniphyllum alkaloids. Chemical Reviews 117: 4104−4146.
2. See for example: (a) Kobayashi J, Kubota T (2009) The Daphniphyllum alkaloids. Natural Product Reports 26: 936–962. (b) Wu H F, Zhang X P, Ding L S, Chen S L, Yang J S, Xu X D (2013) Daphniphyllum alkaloids: Recent findings on chemistry and pharmacology. Planta Medica 79: 1589–1598. (c) Xu J B, Zhang H, Gan L S, Han Y S, Wainberg, M A, Yue J M (2014) Logeracemin A, an anti-HIV Daphniphyllum alkaloid dimer with a new carbon skeleton from Daphniphyllum Longeracemosum. Journal of the American Chemical Society 136: 7631-7633.
3. Zhang Q, Di Y T, Li C S, Fang X, Tan C J, Zhang Z, Zhang Y, He H P, Li S L, Hao X J (2009) Daphenylline, a new alkaloid with an unusual skeleton, from Daphniphyllum Longeracemosum. Organic Letters 11: 2357-2359.
4. (a) Lu Z, Li Y, Deng J, Li A (2013) Total synthesis of the Daphniphyllum alkaloid daphenylline. Nature Chemistry 5: 679-684. (b) Yamada R, Adachi Y, Yokoshima S, Fukuyama T (2016) Total synthesis of (-)-daphenylline. Angewandte Chemie Int. Ed. 55: 6067-6070. (c) Chen X, Zhang H J, Yang X, Lv H, Shao X, Tao C, Wang H, Cheng B, Li Y, Guo J, Zhang J, Zhai H (2018) Divergent total syntheses of (-)-daphnilongeranin B and (-)-daphenylline. Angewandte chemie Int. Ed. 57: 947-951. (d) Chen Y, Zhang W, Ren L, Li J, Li A (2018) Total syntheses of daphenylline, daphnipaxianine A, and himalenine D. Angewandte Chemie Int. Ed. 57:952-956.
5. Wang W, Li G P, Wang S F, Shi Z F, Cao X P (2015) Direct and short construction of the ACDE ring system of daphenylline. Chemistry an Asian Journal 10: 377-382 and the references therein.
6. Diaba F, Pujol-Grau C, Martinez-Laporta A, Fernandez I, Bonjoch J (2015) Synthesis of the Tetracyclic ABCD Ring Systems of Madangamines D-F. Organic Letters 17:568-571.
Faiza Diaba studied chemistry at the University of Constantine, Algeria. She then obtained her PhD. in organic chemistry with Dr. Micheline Grignon-Dubois at Bordeaux I University, France. After a two years postdoctoral position with Prof. Josep Bonjoch at Barcelona University she pursued her scientific career as a lecturer then since 2009 she has been an associate professor at the same University. Her research interests are focused on developing new accessible synthetic methodologies for the synthesis of nitrogen-containing heterocycles directed to the total synthesis of natural compounds using radical chemistry, organocatalysis and electrophilic cyclizations promoted by NIS.