A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2015 Apr 10

PMID 25856767

Citations 23

Authors

Robert J Sharpe

Jeffrey S Johnson

Affiliations

Soon will be listed here.

Abstract

A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C-H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.

Citing Articles

Oxidative cleavage of ketoximes to ketones using photoexcited nitroarenes.

Gottemann L, Wiesler S, Sarpong R Chem Sci. 2023; 15(1):213-219.

PMID: 38131093 PMC: 10732129. DOI: 10.1039/d3sc05414d.

Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery.

Moyo P, Invernizzi L, Mianda S, Rudolph W, Andayi A, Wang M Nat Prod Bioprospect. 2023; 13(1):37.

PMID: 37821775 PMC: 10567616. DOI: 10.1007/s13659-023-00402-2.

Symmetry-Driven Total Synthesis of Myrioneurinol.

Aquilina J, Smith M J Am Chem Soc. 2022; 144(25):11088-11093.

PMID: 35699935 PMC: 9721121. DOI: 10.1021/jacs.2c04487.

The role of biocatalysis in the asymmetric synthesis of alkaloids - an update.

Cigan E, Eggbauer B, Schrittwieser J, Kroutil W RSC Adv. 2022; 11(45):28223-28270.

PMID: 35480754 PMC: 9038100. DOI: 10.1039/d1ra04181a.

Synthesis of rearranged indole diterpenes of the paxilline type.

Schatz D, Kuenstner E, George D, Pronin S Nat Prod Rep. 2021; 39(5):946-968.

PMID: 34931646 PMC: 10122275. DOI: 10.1039/d1np00062d.

References

Neufeldt S, Sanford M . O-acetyl oximes as transformable directing groups for Pd-catalyzed C-H bond functionalization. Org Lett. 2010; 12(3):532-5. PMC: 2830615. DOI: 10.1021/ol902720d. View

Yeung Y, Chein R, Corey E . Conversion of Torgov's synthesis of estrone into a highly enantioselective and efficient process. J Am Chem Soc. 2007; 129(34):10346-7. DOI: 10.1021/ja0742434. View

Nagatomo M, Koshimizu M, Masuda K, Tabuchi T, Urabe D, Inoue M . Total synthesis of ryanodol. J Am Chem Soc. 2014; 136(16):5916-9. DOI: 10.1021/ja502770n. View

Sauer G, Eder U, Haffer G, Neef G, WIECHERT R . Synthesis of D-norgestrel. Angew Chem Int Ed Engl. 1975; 14(6):417. DOI: 10.1002/anie.197504171. View

Siler D, Mighion J, Sorensen E . An enantiospecific synthesis of jiadifenolide. Angew Chem Int Ed Engl. 2014; 53(21):5332-5. PMC: 4153357. DOI: 10.1002/anie.201402335. View

Meng Z, Yu H, Li L, Tao W, Chen H, Wan M . Total synthesis and antiviral activity of indolosesquiterpenoids from the xiamycin and oridamycin families. Nat Commun. 2015; 6:6096. PMC: 4347019. DOI: 10.1038/ncomms7096. View

Breitler S, Carreira E . Total synthesis of (+)-crotogoudin. Angew Chem Int Ed Engl. 2013; 52(42):11168-71. DOI: 10.1002/anie.201305822. View

Goetz A, Silberstein A, Corsello M, Garg N . Concise enantiospecific total synthesis of tubingensin A. J Am Chem Soc. 2014; 136(8):3036-9. PMC: 3985696. DOI: 10.1021/ja501142e. View

Corbett M, Johnson J . Enantioselective synthesis of hindered cyclic dialkyl ethers catalytic oxa-Michael/Michael desymmetrization. Chem Sci. 2014; 4(7):2828-2832. PMC: 3964814. DOI: 10.1039/C3SC51022K. View

10.

Liu L, Chiu P . An expeditious asymmetric synthesis of the pentacyclic core of the cortistatins by an intramolecular (4+3) cycloaddition. Chem Commun (Camb). 2011; 47(12):3416-7. DOI: 10.1039/c1cc00087j. View

11.

Malinowski J, Sharpe R, Johnson J . Enantioselective synthesis of pactamycin, a complex antitumor antibiotic. Science. 2013; 340(6129):180-2. PMC: 3952063. DOI: 10.1126/science.1234756. View

12.

GABBARD R, SEGALOFF A . Structure-activity relationships of estrogens. Effects of 14-dehydrogenation and axial methyl groups at C-7, C-9 and C-11. Steroids. 1983; 41(6):791-805. DOI: 10.1016/0039-128x(83)90054-5. View

13.

Krasovskiy A, Kopp F, Knochel P . Soluble lanthanide salts (LnCl3.2LiCl) for the improved addition of organomagnesium reagents to carbonyl compounds. Angew Chem Int Ed Engl. 2006; 45(3):497-500. DOI: 10.1002/anie.200502485. View

14.

Hajos Z, Parrish D . The stereocontrolled synthesis of trans-hydrindan steroidal intermediates. J Org Chem. 1973; 38(19):3239-43. DOI: 10.1021/jo00959a002. View

15.

MICHELI R, Hajos Z, Cohen N, Parrish D, Portland L, Sciamanna W . Total syntheses of optically active 19-norsteroids. (+)-Estr-4-ene-3,17-dione and (+)13 beta-ethylgon-4-ene-3,17-dione. J Org Chem. 1975; 40(6):675-81. DOI: 10.1021/jo00894a003. View

16.

Wilson B, Wilson C, Hayes A . Tremorgenic toxin from Penicillium cyclopium grown on food materials. Nature. 1968; 220(5162):77-8. DOI: 10.1038/220077b0. View

17.

Adachi M, Higuchi K, Thasana N, Yamada H, Nishikawa T . Stereocontrolled synthesis of an indole moiety of sespendole and stereochemical assignment of the side chain. Org Lett. 2011; 14(1):114-7. DOI: 10.1021/ol202895u. View

18.

IRELAND R, Hengartner U . Studies on the total synthesis of steroidal antibiotics. I. An efficient, stereoselective method for the formation of trans-syn-trans-perhydrophenanthrene derivatives. J Am Chem Soc. 1972; 94(10):3652-3. DOI: 10.1021/ja00765a079. View

19.

Smith 3rd A, Kanoh N, Minakawa N, Rainier J, Blase F, Hartz R . Tremorgenic indole alkaloids. Studies directed toward the assembly of the A, F, and I rings of penitrem D: observation of an unexpected stereochemical outcome. Org Lett. 2000; 1(8):1263-6. DOI: 10.1021/ol9909379. View

20.

Bian M, Wang Z, Xiong X, Sun Y, Matera C, Nicolaou K . Total syntheses of anominine and tubingensin A. J Am Chem Soc. 2012; 134(19):8078-81. DOI: 10.1021/ja302765m. View