Synthesis 2018; 50(03): 663-675
DOI: 10.1055/s-0036-1589132
paper
© Georg Thieme Verlag Stuttgart · New York

Studies on the Total Synthesis of Antibiotic Macrolactin S: A Conventional Approach for the Synthesis of the C1–C9 and C10–C24 Fragments

Ramakrishna Sayini
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India   Email: srihari@iict.res.in
,
Pabbaraja Srihari*
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India   Email: srihari@iict.res.in
› Author Affiliations
S.R. thanks UGC, New Delhi for financial support. The authors thank CSIR, New Delhi, for funding through the XII Five-Year Plan Programme under budget head CSC-0108.
Further Information

Publication History

Received: 27 August 2017

Accepted after revision: 18 October 2017

Publication Date:
16 November 2017 (online)


Abstract

The C1–C9 and C10–C24 segments of the 24-membered polyene macrolide macrolactin S were synthesized by routes involving an epoxide-ring-opening reaction, an Ohira–Bestmann alkyne formation, a chelation-controlled nucleophilic addition reaction, and a Still–Gennari olefination as key steps. A chiron approach , starting from readily available glucose diacetonide, was used to synthesize a key intermediate, and a convergent approach was adopted for the synthesis of the key C10–C24 fragment.

Supporting Information

 
  • References

    • 1a Pereira RB. Andrade PB. Valentão P. Mar. Drugs 2016; 14: 1
    • 1b Blunt JW. Copp BR. Keyzers RA. Munro MH. Prinsep MR. Nat. Prod. Rep. 2015; 32: 116
    • 1c Newmann DJ. Cragg GM. J. Nat. Prod. 2012; 75: 311
    • 1d Martins A. Vieira H. Gaspar H. Santos S. Mar. Drugs 2014; 12: 1066
  • 2 Lu XL. Xu QZ. Shen YH. Liu XY. Jiao BH. Zhang WD. Ni KY. Nat. Prod. Res. 2008; 22: 342
    • 3a Yadav JS. Raj Kumar M. Sabitha G. Tetrahedron Lett. 2008; 49: 463
    • 3b Yadav JS. Gupta MK. Prathap I. Synthesis 2007; 1343
    • 3c Kobayashi Y. Fukuda A. Kimachi T. Ju-ichi M. Takemoto Y. Tetrahedron Lett. 2004; 45: 677
    • 3d Li S. Xu R. Bai D. Tetrahedron Lett. 2000; 41: 3463
    • 3e Boyce RJ. Pattenden G. Tetrahedron Lett. 1996; 37: 3501
    • 4a Marino JP. McClure MS. Holub DP. Comasseto JV. Tucci FC. J. Am. Chem. Soc. 2002; 124: 1664
    • 4b Kim Y. Singer RA. Carreira EM. Angew. Chem. Int. Ed. 1998; 37: 1261
    • 4c Smith AB. III. Ott GR. J. Am. Chem. Soc. 1998; 120: 3935
    • 4d Smith AB. III. Ott GR. J. Am. Chem. Soc. 1996; 118: 13095
    • 5a Sankara Rao P. Srihari P. Org. Biomol. Chem. 2016; 14: 9629
    • 5b Yadav JS. Suresh B. Srihari P. Eur. J. Org. Chem. 2016; 2509
    • 5c Yadav JS. Suresh B. Srihari B. Eur. J. Org. Chem. 2015; 5856
    • 5d Sridhar Y. Srihari P. Org. Biomol. Chem. 2014; 12: 2950
    • 5e Yadav JS. Singh VK. Srihari P. Org. Lett. 2014; 16: 836
    • 5f Sridhar P. Srihari P. Org. Biomol. Chem. 2013; 11: 4640
    • 5g Sridhar Y. Srihari P. Eur. J. Org. Chem. 2013; 578
  • 6 Yadav JS. Prathap I. Tadi BP. Tetrahedron Lett. 2006; 47: 3773
  • 7 Still WC. McDonald JH. III. Tetrahedron Lett. 1980; 21: 1031
  • 8 Hoye TR. Jeffrey CS. Shao F. Nat. Protoc. 2007; 2: 2451
  • 9 Dess DB. Martin JC. J. Am. Chem. Soc. 1991; 113: 7277
    • 10a Yamaguchi M. Hirao I. Tetrahedron Lett. 1983; 24: 391
    • 10b Sharma GV. M. Mallesham S. Chandra Mouli C. Tetrahedron: Asymmetry 2009; 20: 2513
    • 11a Jacobi PA. Guo J. Rajeswari S. Zheng W. J. Org. Chem. 1997; 62: 2907
    • 11b Rollin P. Tetrahedron Lett. 1986; 27: 4169
  • 12 Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002; 2563 ; Our attempts without HMPA resulted in a 1:1 mixture of diastereomers
    • 14a Ando K. J. Org. Chem. 1997; 62: 1934
    • 14b Still WC. Gennari C. Tetrahedron Lett. 1983; 24: 4405
  • 15 Zhang HX. Buibe F. Balavoine G. J. Org. Chem. 1990; 55: 1857
  • 16 Although total consumption of the starting material was observed, we ended up with the acetonide-deprotected compound rather than the required iodinated compound.
  • 17 Reddy CR. Suman D. Rao NN. Helv. Chim. Acta 2015; 98: 967
  • 18 The product was difficult to isolate, as a number of spots appeared on the TLC.