Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives

Wei Li, Dong Jin Hwang, Dieter Cremer, Hyun Joo, Elfi Kraka, Juhyun Kim, Charles R. Ross, Viet Q. Nguyen, James T. Dalton, Duane Miller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We report on the synthesis and investigation of two diastereomers (5a and 5b) of a new bicalutamide analog with an asymmetric carbon atom and a chiral sulfoxide group. These bicalutamide analogs are novel androgen receptor antagonists with biological activities that depend significantly on the configuration of their stereogenic centers. We determined the absolute configuration at the SO center by combining X-ray and NMR measurements with quantum chemical calculations. Since 5a and 5b failed to yield satisfactory crystals for X-ray crystal structure determination, analogs 6a and 6b differing in only one remote functional group relative to the chiral sulfoxide were synthesized, which yielded satisfactory crystals. X-ray structure determination of 6a and 6b provided the absolute configuration at the chiral sulfoxide. Since the structural difference between 5 and 6 is remote from the chiral sulfoxide, the structural assignment was extended from the diastereomers of 6 to those of 5 provisionally. These assignments were verified with the help of measured and DFT-calculated proton and carbon NMR chemical shifts.

Original languageEnglish (US)
Pages (from-to)578-583
Number of pages6
JournalChirality
Volume21
Issue number6
DOIs
StatePublished - Aug 12 2009

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sulfoxide
Derivatives
X rays
X-Rays
Nuclear magnetic resonance
Crystals
Carbon
Androgen Receptor Antagonists
Chemical shift
Bioactivity
Discrete Fourier transforms
Functional groups
Protons
Crystal structure
Atoms
bicalutamide

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives. / Li, Wei; Hwang, Dong Jin; Cremer, Dieter; Joo, Hyun; Kraka, Elfi; Kim, Juhyun; Ross, Charles R.; Nguyen, Viet Q.; Dalton, James T.; Miller, Duane.

In: Chirality, Vol. 21, No. 6, 12.08.2009, p. 578-583.

Research output: Contribution to journalArticle

Li, W, Hwang, DJ, Cremer, D, Joo, H, Kraka, E, Kim, J, Ross, CR, Nguyen, VQ, Dalton, JT & Miller, D 2009, 'Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives', Chirality, vol. 21, no. 6, pp. 578-583. https://doi.org/10.1002/chir.20642
Li, Wei ; Hwang, Dong Jin ; Cremer, Dieter ; Joo, Hyun ; Kraka, Elfi ; Kim, Juhyun ; Ross, Charles R. ; Nguyen, Viet Q. ; Dalton, James T. ; Miller, Duane. / Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives. In: Chirality. 2009 ; Vol. 21, No. 6. pp. 578-583.
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AU - Kraka, Elfi

AU - Kim, Juhyun

AU - Ross, Charles R.

AU - Nguyen, Viet Q.

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