Total Syntheses of HMP-Y1, Hibarimicinone, and HMP-P1

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2012 Sep 14

PMID 22970979

Citations 11

Authors

Brian B Liau

Benjamin C Milgram

Matthew D Shair

Affiliations

Soon will be listed here.

Abstract

Total syntheses of HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone, and HMP-P1 are described using a two-directional synthesis strategy. A novel benzyl fluoride Michael-Claisen reaction sequence was developed to construct the complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical, two-directional, double annulation. Through efforts to convert HMP-Y1 derivatives to hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected HMP-Y1 was realized. A two-directional unsymmetrical double annulation and biomimetic etherification was developed to construct the polycyclic and highly oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. The use of a racemic biaryl precursor allowed for the synthesis of both hibarimicinone atropisomers and provides the first confirmation of the structure of atrop-hibarimicinone. Additionally, this work documents the first reported full characterization of atrop-hibarimicinone, HMP-Y1, atrop-HMP-Y1, and HMP-P1. Last, a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was discovered, which provides valuable information necessary to achieve syntheses of the glycosylated congeners of hibarimicinone.

Citing Articles

Speciation and kinetics of fluoride transfer from tetra--butylammonium difluorotriphenylsilicate ('TBAT').

Kucharski M, Watson A, Lloyd-Jones G Chem Sci. 2024; 15(12):4331-4340.

PMID: 38516098 PMC: 10952091. DOI: 10.1039/d3sc05776c.

Synthetic studies directed toward the AB decalin common to HMP-Y1 and hibarimicinone.

Hempel J, Engers D, Sulikowski G Tetrahedron Lett. 2020; 55(13):2157-2159.

PMID: 32855575 PMC: 7449242. DOI: 10.1016/j.tetlet.2014.02.069.

Both d- and l-Glucose Polyphosphates Mimic d--Inositol 1,4,5-Trisphosphate: New Synthetic Agonists and Partial Agonists at the Ins(1,4,5)P Receptor.

Shipton M, Riley A, Rossi A, Brearley C, Taylor C, Potter B J Med Chem. 2020; 63(10):5442-5457.

PMID: 32286062 PMC: 7260056. DOI: 10.1021/acs.jmedchem.0c00215.

Development of a Cross-Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)-ABX.

Huang J, Shia K Angew Chem Int Ed Engl. 2020; 59(16):6540-6545.

PMID: 31944523 PMC: 7187479. DOI: 10.1002/anie.201914657.

Enantioselective Ruthenium-Catalyzed Benzocyclobutenone-Ketol Cycloaddition: Merging C-C Bond Activation and Transfer Hydrogenative Coupling for Type II Polyketide Construction.

Ambler B, Turnbull B, Suravarapu S, Uteuliyev M, Huynh N, Krische M J Am Chem Soc. 2018; 140(29):9091-9094.

PMID: 29992811 PMC: 6226000. DOI: 10.1021/jacs.8b05724.

References

Kim K, Maharoof U, Raushel J, Sulikowski G . Diverging stereochemical pathways in an intramolecular Diels-Alder reaction determined by dienophile structure. Org Lett. 2003; 5(16):2777-80. DOI: 10.1021/ol034823f. View

Cho S, Fukazawa H, Honma Y, Kajiura T, Hori H, Igarashi Y . Effects of hibarimicins and hibarimicin-related compounds produced by Microbispora on v-Src kinase activity and growth and differentiation of human myeloid leukemia HL-60 cells. J Antibiot (Tokyo). 2002; 55(3):270-8. DOI: 10.7164/antibiotics.55.270. View

Uehara Y, Li P, Fukazawa H, Mizuno S, Nihei Y, Nishio M . Angelmicins, new inhibitors of oncogenic src signal transduction. J Antibiot (Tokyo). 1993; 46(8):1306-8. DOI: 10.7164/antibiotics.46.1306. View

Lee H, Ahn J, Lee A, Shair M . Enantioselective synthesis of the lomaiviticin aglycon full carbon skeleton reveals remarkable remote substituent effects during the dimerization event. Chemistry. 2010; 16(44):13058-62. PMC: 3152949. DOI: 10.1002/chem.201002157. View

HAUSER F, Gauuan P . Total synthesis of (+/-)-biphyscion. Org Lett. 2000; 1(4):671-2. DOI: 10.1021/ol990758r. View

Hori H, Kajiura T, Igarashi Y, Furumai T, Higashi K, Ishiyama T . Biosynthesis of hibarimicins. I. 13C-labeling experiments. J Antibiot (Tokyo). 2002; 55(1):46-52. DOI: 10.7164/antibiotics.55.46. View

Huang X, Xue J . A novel multicomponent reaction of arynes, beta-keto sulfones, and michael-type acceptors: a direct synthesis of polysubstituted naphthols and naphthalenes. J Org Chem. 2007; 72(10):3965-8. DOI: 10.1021/jo070241q. View

Mal D, Pahari P . Recent advances in the Hauser annulation. Chem Rev. 2007; 107(5):1892-918. DOI: 10.1021/cr068398q. View

Kajiura T, FURUMAI T, Igarashi Y, Hori H, Higashi K, Ishiyama T . Signal transduction inhibitors, hibarimicins, A, B, C, D and G produced by Microbispora. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties. J Antibiot (Tokyo). 1998; 51(4):394-401. DOI: 10.7164/antibiotics.51.394. View

10.

Hori H, Igarashi Y, Kajiura T, FURUMAI T, Higashi K, Ishiyama T . Signal transduction inhibitors, hibarimicins A, B, C, D and G produced by Microbispora. II. Structural studies. J Antibiot (Tokyo). 1998; 51(4):402-17. DOI: 10.7164/antibiotics.51.402. View

11.

Narayan S, Roush W . Studies toward the total synthesis of angelmicin B (hibarimicin B): synthesis of a model CD-D' arylnaphthoquinone. Org Lett. 2004; 6(21):3789-92. DOI: 10.1021/ol048436x. View

12.

BITHA P, HLAVKA J, Boothe J . 6-Fluorotetracyclines. J Med Chem. 1970; 13(1):89-92. DOI: 10.1021/jm00295a023. View

13.

Romaine I, Hempel J, Shanmugam G, Hori H, Igarashi Y, Polavarapu P . Assignment and stereocontrol of hibarimicin atropoisomers. Org Lett. 2011; 13(17):4538-41. PMC: 3163008. DOI: 10.1021/ol2017005. View

14.

Milgram B, Liau B, Shair M . Gram-scale synthesis of the A'B'-subunit of angelmicin B. Org Lett. 2011; 13(24):6436-9. PMC: 3237735. DOI: 10.1021/ol202728v. View

15.

Lee W, Kim K, Sulikowski G . Studies into the stereoselectivity of tartrate-derived dienophiles. Org Lett. 2005; 7(9):1687-9. DOI: 10.1021/ol050105c. View

16.

Kummer D, Li D, Dion A, Myers A . A practical, convergent route to the key precursor to the tetracycline antibiotics. Chem Sci. 2011; 2(9):1710-1718. PMC: 3176682. DOI: 10.1039/C1SC00303H. View

17.

Lambert W, Roush W . Synthesis of the A-B subunit of angelmicin B. Org Lett. 2005; 7(24):5501-4. DOI: 10.1021/ol052321r. View

18.

Li J, Todaro L, Mootoo D . Synthesis of an A'B' Precursor to Angelmicin B: Product Diversification in the Suárez Lactol Fragmentation. European J Org Chem. 2012; 2011(31):6281-6287. PMC: 3383051. DOI: 10.1002/ejoc.201100815. View

19.

Sun C, Wang Q, Brubaker J, Wright P, Lerner C, Noson K . A robust platform for the synthesis of new tetracycline antibiotics. J Am Chem Soc. 2008; 130(52):17913-27. PMC: 2681267. DOI: 10.1021/ja806629e. View

20.

Nicolaou K, Hwee Lim Y, Piper J, Papageorgiou C . Total syntheses of 2,2'-epi-cytoskyrin A, rugulosin, and the alleged structure of rugulin. J Am Chem Soc. 2007; 129(13):4001-13. DOI: 10.1021/ja0685708. View