US 2020/0048233 A1Published application

Cyclization processes of hydroxyalkenoic aicds and products thereof

AssigneeYissum Research Development Company of the Hebrew University of Jerusalem

InventorDmitry TSVELIKHOVSKY

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Abstract

The invention provides efficient cyclization processes of hydroxyalkenoic acids and products produced therefrom. The following reactions are claimed: Formula (I), (II), (V) and (VI).

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Claims21

Dependent claims

A process for the preparation of compound of formula comprising the step of:

Reacting compound of formula (I) in the presence of at least one Pd catalyst and at least one base;
R1 and R2 are each independently selected from a group consisting of H, straight or branched C1-C15 alkyl, straight or branched C2-C15 alkenyl, straight or brandied C2-C15 alkynyl, C5-C12 aryl, C5-C12 heteroaryl;
C3-C12 cycloalkyl, C3-C12 heterocycloalkyl;
each optionally substituted by at least one OH, amine, amide, halide, straight or branched C1-C15 alkyl, straight or branched C2-C15 alkenyl, straight or branched C2-C15 alkynyl, —O(C1-C8 akyl), —OC(═O)(C1-C8 alkyl), —C(═O)(C4-C8 alkyl), —C(═O)O(C1-C8 alkyl);
C5-C12 aryl, C5-C12 heteroaryl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl;
R3 and R4 are H;
and n is an integer being 1-6.

4 more elements

Dependencies are inferred from the claim text.

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Abstract

The invention provides efficient cyclization processes of hydroxyalkenoic acids and products produced therefrom. The following reactions are claimed: Formula (I), (II), (V) and (VI).

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Claims21

Dependent claims

A process for the preparation of compound of formula comprising the step of:

Reacting compound of formula (I) in the presence of at least one Pd catalyst and at least one base;
R1 and R2 are each independently selected from a group consisting of H, straight or branched C1-C15 alkyl, straight or branched C2-C15 alkenyl, straight or brandied C2-C15 alkynyl, C5-C12 aryl, C5-C12 heteroaryl;
C3-C12 cycloalkyl, C3-C12 heterocycloalkyl;
each optionally substituted by at least one OH, amine, amide, halide, straight or branched C1-C15 alkyl, straight or branched C2-C15 alkenyl, straight or branched C2-C15 alkynyl, —O(C1-C8 akyl), —OC(═O)(C1-C8 alkyl), —C(═O)(C4-C8 alkyl), —C(═O)O(C1-C8 alkyl);
C5-C12 aryl, C5-C12 heteroaryl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl;
R3 and R4 are H;
and n is an integer being 1-6.

4 more elements

Dependencies are inferred from the claim text.

Description10,282 words

Summary2,290 words

#The present invention is in the field of cyclization processes of hydroxyalkenoic acids and products produced therefrom.

#References considered to be relevant as background to the presently disclosed subject matter are listed below: [1] S. Baskaran, Imadul Islam, S. Chandrasekaran, J. Org. Chem. 1990, 55, 891-895. [2] A. A. H. El-Gamal, S. K. Wang, C. Y. Duh, Org. Lett. 2005, 7, 2023-2025. [3] S. C. Gupta, R. Kannappan, J. Kim, G. M. Rahman, S. K. Francis, R. Raveendran, M. S. Nair, J. Das, B. B. Aggarwal, Mol. Pharmacol. 2011, 80, 769-81. [4] K. Harada, H. Ito, H. Hioki, Y. Fukuyama, Tetrahedron Lett. 2007, 48, 6105-6108. [5] R. A. Macahig, L. Harinantenaina, K. Matsunami, H. Otsuka, Y. Takeda, T. Shinzato, J. Nat. Med. 2010, 64, 1-8. [6] E. Mousouri, E. Melliou, P. Magiatis, J. Agric. Food Chem. 2014, 62, 660-667. [7] B. M. Trost, J. M. Balkovec, M. K. T. Mao, J. Am. Chem. Soc. 1986, 4974-4983. [8] H. Lee, M. Chung, C. Lee, B. Yun, H. Chun, Y. Kho, J. Antibiot. (Tokyo). 1996, 50, 357-359. [9] A. Ortega, J. D. E. L. C. Lopez, E. Maldonado, I. De Quimtca, U. Nactonal, A. De Mixtco, C. Extertor, C. Umversitana, Phytochemistry 1989, 28, 2735-2736. [10] C. M. Thompson, C. A. Quinn, P. J. Hergenrother, J. Med. Chem. 2009, 52, 117-125. [11] M. Braun, T. Meier, Angew. Chemie—Int. Ed. 2006, 45, 6952-6955. [12] J. Tsuji, Palladium Reagents and Catalysts, 2004. [13] B. Trost, T. Dietsch, J. Am. Chem. Soc. 1973, 95, 8200-8201. [14] B. M. Trost, Angew. Chem. Int. Ed. Engl. 1989, 28, 1173-1192. [15] H. Kinoshita, H. Shinokubo, K. Oshima, Org. Lett. 2004, 6, 4085-4088. [16] Y. Hanzawa, S. Ishizawa, H. Ito, Y. Kobayashi, T. Taguchi, J. Chem. Soc. Chem. Commun. 1990, 5, 394-395. [17] T. Sengoku, T. Hamamatsu, T. Inuzuka, M. Takahashi, M. Science, F. Engineering, Synlett 2011, 12, 1766-1768. [18] Y. Suzuki, T. Seki, S. Tanaka, M. Kitamura, J. Am. Chem. Soc. 2015, 137, 9539-9542. [19] S. Y. Ko, E. Oh, J. C. Park, J. U. Yoo, Helv. Chim. Acta 2002, 85, 3994-3999. [20] H. T. Chang, T. J. Thiruvellore, C. C. Wang, C. H. Cheng, J. Am. Chem. Soc. 2007, 129, 12032-12041. [21] M. Chakravarty, K. C. K. Swamy, J. Org. Chem. 2006, 71, 9128-9138. [22] M. Arthuis, R. Pontikis, G. G. Chabot, J. Seguin, L. Quentin, S. Bourg, L. Morin-Allory, J. C. Florent, ChemMedChem 2011, 6, 1693-1705. [23] J. Kratochvil, Z. Novák, M. Ghavre, L. Nováková, A. Růžička, J. Kuneš, M. Pour, Org. Lett. 2015, 17, 520-523. [24] P. J. Guiry, Adv. Synth. Catal. 2007, 349, 2407-2424. [25] R. E. Taylor, J. P. Ciavarri, Org. Lett. 1999, 1, 467-469. [26] O. A. Abdelrahman, A. Heyden, J. Q. Bond, ACS Catal. 2014, 4, 1171-1181. [27] K. Mori, Tetrahedron 1985, 41, 919-925. [28] Y. Mazur, N. Danieli, F. Sondheimer, J. Am. Chem. Soc. 1960, 82, 5889-5908. [29] L. Yet, Chem. Rev. 2000, 100, 2963-3007. [30] T. Kurihara, Y. Nakajima, O. Mitsunobu, Tetrahedron Lett. 1976, 17, 2455-2458. [31] H. M. C. Ferraz, F. I. Bombonato, M. K. Sano, L. S. Longo, Quim. Nova 2008, 31, 885-900. [32] I. Shiina, Chem. Rev. 2007, 107, 239-273. [33] R. C. Larock, T. R. Hightower, J. Org. Chem. 1993, 58, 5298-5300. [34] R. M. Trend, Y. K. Ramtohul, E. M. Ferreira, B. M. Stoltz, Angew. Chemie—Int. Ed. 2003, 42, 2892-2895. [35] P. F. Li, H. L. Wang, J. Qu, J. Org. Chem. 2014, 79, 3955-3962. [36] D. H. Birtwistle, J. M. Brown, M. W. Foxton, Tetrahedron 1988, 44, 7309-7318.

#Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.

Detailed description7,992 words

#The spontaneous condensation of hydroxyalkenoic acid 1, generating methylene lactone of Type-2 is well known. [11-14] Inevitably, to obtain methylene (n)-lactone 4, the condensation pathway has to be suppressed. The inventors have found that a necessary diversion of the reaction pathway can take place under Pd(0) Tsuji-Trost conditions via intermediate 3 (as shown in Scheme 2).

#In the present invention Pd Tsuji-Trost allylation, taking place in the presence of free alcohol and free carboxylic acid as a nucleophile (see structure of 1) was employed The invention further provides the construction process of methylene lactone scaffolds of Type-4 (and its structural analogues).

#The condensation suppression makes it possible to produce γ-lactone 6, via intermediate 5 (roving the palladium π-allyl complex), as shown in Scheme 2.

Abstract

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Claims21

Abstract

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Claims21

Description10,282 words

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Classification15 codes

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Description10,282 words