54706-99-9Relevant articles and documents
Identification, structural modification, and dichotomous effects on human immunodeficiency virus type 1 (HIV-1) replication of ingenane esters from Euphorbia kansui
Liu, Qingbo,Li, Wei,Huang, Li,Asada, Yoshihisa,Morris-Natschke, Susan L.,Chen, Chin-Ho,Lee, Kuo-Hsiung,Koike, Kazuo
supporting information, p. 618 - 627 (2018/07/29)
Euphorbia kansui showed potent anti-HIV-1 activity during screening of a library composed of plant extracts from Euphorbiaceae and Thymelaeaceae families. Bioassay-guided isolation led to identification of ingenane esters as the active compounds. Further chemical modification resulted in 3-(2-naphthoyl)ingenol (23), which exhibited the most potent anti-HIV-1 activity. Compound 23 also acted as an HIV-1-latency-reversing agent on activation of HIV-1 replication in a latently infected U1 cell model and a T cell latent HIV-1 model JLat-A2.
METHODS OF SYNTHESIS OF INGENOL AND INTERMEDIATES THEREOF
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, (2014/12/12)
The present invention relates generally to methods of synthesis of diterpene heterocylic compounds. More particularly, the present invention relates to efficient methods of synthesis of ingenol (Formula (21), CAS 30220-46-3), from a compound of formula (1). The present invention also provides for various advantageous intermediates along the synthetic route of ingenol. Efficient synthesis of ingenol is important in the design and synthesis of related analogues, such as ingenol-3-angelate.
Development of a concise synthesis of (+)-ingenol
McKerrall, Steven J.,J?rgensen, Lars,Kuttruff, Christian A.,Ungeheuer, Felix,Baran, Phil S.
, p. 5799 - 5810 (2014/05/06)
The complex diterpenoid (+)-ingenol possesses a uniquely challenging scaffold and constitutes the core of a recently approved anti-cancer drug. This full account details the development of a short synthesis of 1 that takes place in two separate phases (cyclase and oxidase) as loosely modeled after terpene biosynthesis. Initial model studies establishing the viability of a Pauson-Khand approach to building up the carbon framework are recounted. Extensive studies that led to the development of a 7-step cyclase phase to transform (+)-3-carene into a suitable tigliane-type core are also presented. A variety of competitive pinacol rearrangements and cyclization reactions were overcome to develop a 7-step oxidase phase producing (+)-ingenol. The pivotal pinacol rearrangement is further examined through DFT calculations, and implications for the biosynthesis of (+)-ingenol are discussed.
14-Step synthesis of (+)-ingenol from (+)-3-carene
Jorgensen, Lars,McKerrall, Steven J.,Kuttruff, Christian A.,Ungeheuer, Felix,Felding, Jakob,Baran, Phil S.
, p. 878 - 882 (2013/09/12)
Ingenol is a diterpenoid with unique architecture and has derivatives possessing important anticancer activity, including the recently Food and Drug Administration-approved Picato, a first-in-class drug for the treatment of the precancerous skin condition actinic keratosis. Currently, that compound is sourced inefficiently from Euphorbia peplus. Here, we detail an efficient, highly stereocontrolled synthesis of (+)-ingenol proceeding in only 14 steps from inexpensive (+)-3-carene and using a two-phase design. This synthesis will allow for the creation of fully synthetic analogs of bioactive ingenanes to address pharmacological limitations and provides a strategic blueprint for chemical production. These results validate two-phase terpene total synthesis as not only an academic curiosity but also a viable alternative to isolation or bioengineering for the efficient preparation of polyoxygenated terpenoids at the limits of chemical complexity.
Total synthesis of ingenol
Nickel, Andrew,Maruyama, Toru,Tang, Haifeng,Murphy, Prescott D.,Greene, Blake,Yusuff, Naeem,Wood, John L.
, p. 16300 - 16301 (2007/10/03)
A total synthesis of the biologically important diterpene ingenol has been completed. Ring-closing olefin metathesis was used to construct the strained "inside-outside" tetracyclic skeleton, and a series of diastereoselective reactions were employed to complete the synthesis. Another naturally occurring ingenane, 20-deoxyingenol, has also been prepared. Copyright
