3-Methoxysulfoxide-(2R,3R)-threoninyl desoxazoline-ascidiacyclamide
3-Methoxysulfoxide-(2R,3R)-threoninyl desoxazoline-ascidiacyclamide

[Thz=thiazole, Ms=-0SO2OMe, Thr=(2S,3R), D-alloThr=(2R,3R)]

RasMol2.7.2.1, and stucked by GifBuilder (Yves Piguet, 1997)
X-Ray diffraction data were measured on SPring-8/BL24XU-A with the approval from Hyogo Prefecture and Japan Synchrotron Radiation Research Institute (C00A24XU-5003N).
Reference: Copyright © International Union of Crystallography
Doi, M., Asano, A., Usami, Y., Katsuya, Y., Nakai, M., Sasaki, M., Taniguchi, T. and Hasegawa, H. (2001). A folded conformation of an ascidiacyclamide derivative: 3-methoxysulfoxide-(2R,3R)-threoninyl desoxazoline-ascidiacyclamide. Acta Crystallogr. E57, o1019-o1021.

See also Index of Section E.

    Ascidiacyclamide (ASC) (3) is a symmetric cyclic peptide (Fig.1) containing unusual amino acids such as oxazoline (Oxz) and thiazole (Thz). Two major conformations and their conformational equilibrium have been suggested for ASC. In our series of studies, the relationships between ASC conformation and symmetry of the chemical structure have been examined; additionally we have studied the asymmetric modifications which disturb the C2-symmetry of ASC and how this affects the ASC structures in both the solid state and in solution. Here, we extend the asymmetric modifications by substituting the Oxz residues with their diastereomers.

    ASC is synthesized from a cyclic hexapeptide, (1), using thionyl chloride , as shown in Fig.1. Oxz rings are formed from the threonine residues via the chlorosulfoxide intermediate (2) after reacting for 1-2 days at 0-4 C. For synthesis of the ASC diastereomers, the threonine residues of (1) are replaced by the following threonine diastereomers: Thr, allo-threonine (aThr), D-Thr and D-aThr. A total of ten diastereomers of (1) were synthesized and their configurations at positions (10,11,41,42) are (S,S,S,S), (S,S,S,R), (S,S,R,R) , (S,S,R,S), (S,R,S,R), (S,R,R,R), (S,R,R,S), (R,R,R,R), (R,R,R,S) and (R,S,R,S). Natural ASC is synthesized from (S,S,S,S)-(1).

    For seven of the ten diastereomers, the reaction of Oxz formation was completed under the reported conditions. However, this reaction did not complete or delayed for the three diastereomers having (R,R,R,R), (R,R,R,S) and (R,S,R,S) configurations. These configurations imply that residues 2 and 6 are D-amino acids (Ca at positions 10 and 41). We presume that a particular conformation, which hinders the completion of the reaction, is present in the intermediates (2) derived from these three diastereomers. Such a conformation is interesting because it is stable, even in thionyl chloride solution. To clarify this conformation, three methyl sulfoxide derivatives of 4 were isolated, by the addition of methanol to intermediates (2), and the structure of (R,R,R,R)-(4) was analyzed.

PLATON (Spek,1998) drawing

X-Ray Data Summary

formulaC38 H60 N8 O12 S4
space groupP212121
Cell Crystal
a (Ang) 10.7820(3)  description block
b (Ang) 19.6026(4) colour colorless
c (Ang) 22.5181(7)size (mm3) 0.08x0.08x0.08
alpha (deg) 90.0 Dx (g/ml) 1.325
beta (deg) 90.0F(000) 2016
gamma (deg) 90.0 mu (mm-1) 0.265
V (Ang^3) 4759.3(2)
Z 4
Refinement Diffrn measurement
Flack 0.38(15)device typeRigaku RAXIS-IV
parameters 560 decay ---
restraints 0 index limit-13-h-13,-23-k-23,0-L-27
R_factor_all 0.0783Rint 0.0554
R_factor_gt 0.0750reflections(meas) 4973 merged form 16269
wR_factor_ref0.2592reflections(merged) 4759 .gt. 2sigma(I)
wR_factor_gt 0.2583Structure
shift/su_max 0.042solution SHELXS-97
shift/su_mean 0.004 refinement SHELXL-97

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Date: Nov. 2001