144681-75-4Relevant academic research and scientific papers
Total synthesis of the actinoallolides and a designed photoaffinity probe for target identification
Anketell, Matthew J.,Paterson, Ian,Sharrock, Theodore M.
, p. 8109 - 8118 (2020)
The actinoallolides are a family of polyketide natural products isolated from the bacterium Actinoallomurus fulvus. They show potent biological activity against trypanosomes, the causative agents of the neglected tropical diseases human African trypanosomiasis (sleeping sickness) and Chagas disease, while exhibiting no cytotoxicity against human cell lines. Herein, we give a full account of our strategy evolution towards the synthesis of this structurally unique class of 12-membered macrolides, which culminated in the first total synthesis of (+)-actinoallolide A in 20 steps and 8% overall yield. Subsequent late-stage diversification then provided ready access to the congeneric (+)-actinoallolides B-E. Enabled by this flexible and efficient endgame sequence, we also describe the design and synthesis of a photoaffinity probe based on actinoallolide A to investigate its biological mode of action. This will allow ongoing labelling studies to identify their protein binding target(s). This journal is
Applications of crotyldiisopinocampheylboranes in synthesis: A formal total synthesis of (+)-calyculin A
Anderson, Oren P.,Barrett, Anthony G.M.,Edmunds, Jeremy J.,Hachiya, Shun-Ichiro,Hendrix, James A.,Horita, Kiyoshi,Malecha, James W.,Parkinson, Christopher J.,Vansickle, Andrew
, p. 1562 - 1592 (2007/10/03)
The formal total synthesis of the marine metabolite (+)-calyculin A is reported. The key steps involve (i) the use of Brown allylboration chemistry to control the relative and absolute stereochemistry of homoallylic alcohol arrays, thus setting eight of the desired stereocenters; (ii) Stille coupling methodology in the construction of the cyano tetraene unit of the natural product; and (iii) a modified Cornforth-Meyers approach to the synthesis of the oxazole fragment.
Total Synthesis of Tautomycin
Oikawa, Masato,Ueno, Tohru,Oikawa, Hideaki,Ichihara, Akitami
, p. 5048 - 5068 (2007/10/02)
A convergent stereocontrolled synthesis of the antifungal antibiotic tautomycin, a potent protein phosphatases inhibitor, has been achieved first via key aldol coupling of two large subunits, a right-hand C1-C21 ketone and a left-hand aldehyde (left from C22).The C1-C10 segment was synthesized through a remote stereochemical control process using a spiroketal template.After joining with the C11-C18 segment, the spiroketal moiety was selectively constructed.Then the right-hand C1-C21 ketone was synthesized via Roush asymmetric crotylboration.The left-hand aldehyde was prepared from a C21-C26 segment and a dialkylmaleic anhydride segment.Completely stereoselective assemblage of the two subunits, the right-hand and the left-hand, was achieved by employing the Mukaiyama aldol reaction.Further functional group manipulation including desilylation, oxidation at C2, and deprotection of tert-butyl ester with concomitant anhydride formation provided tautomycin which was identical with the natural product.As a preliminary study, derivatizations and degradation of the natural product were also examined to support the total synthesis.
