Conformation and synthesis of diketopiperazines. 3,4-Dehydroproline anhydride

Karle, Isabella L.; Ottenheym, H. C. J.; Witkop, B.

doi:10.1021/ja00809a033

Cited by 32 publications

(12 citation statements)

References 2 publications

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“…Clearly, the different asphericity of the atoms in the glycine residue and the proline residue is responsible for the different carbonyl bond lengths obtained from the full-data refinement. In addition, it is interesting to note that the proline carbonyl bond length from the full-data refinement of 3,4-dehydroproline anhydride (Karle, Ottenheym & Witkop, 1974) is exactly the same, 1.228 A, as those obtained from both full-data refinements of proline DKP compounds. In a similar way, all the C-C bonds except CIB-C1 become virtually identical at 1.518 A in the high-angle refinement while the full-data refinement showed C~-C~ to be distinctly shorter at 1.504 (3) A.…”

Section: Discussionmentioning

confidence: 75%

The crystal structure of cyclo-L-prolylglycyl: a refinement of high-angle diffraction data

Dreele¹

1975

Acta Crystallogr Sect B

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The structure of cyclo-L-prolyl-glycyl has been determined by single-crystal X-ray analysis. The crystals are orthorhombic, space group P212121, a = 9-666 +_ 0.006, b = 5.780 + 0.004, c = 13-067 + 0.010/~, and Z=4. Diffractometer data were collected using monochromated Mo K~ radiation and the structure was refined with the entire data set to give the residuals R=0.044 and Rw=0.051. A refinement using only the high-angle data (sin 0/2_> 0.40) gave the residuals R=0.049 and Rw=0.046. Both the diketopiperazine ring and the pyrrolidine ring are appreciably puckered and the molecular conformation is virtually identical to that of cyclo-L-prolyl-L-leucyl [Karle, I. L. (1972). J. Amer. Chem. Soc. 94,[81][82][83][84]. Marked differences in the parameters are noted for the two refinements with the high-angle refinement giving generally identical distances for chemically similar bonds. Similarly the high-angle results indicate less apparent thermal motion of the molecule than does the full-data refinement.

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Section: Discussionmentioning

confidence: 75%

The crystal structure of cyclo-L-prolylglycyl: a refinement of high-angle diffraction data

Dreele¹

1975

Acta Crystallogr Sect B

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“…A comparison of the dihedral angle between the planes through the atoms [N(2),C(1),C(2)J and the least-squares plane through the atoms [N( 1),C(2),N(2),C(4)] in 2 (36°) and the C(l)-mercapto-C(3)-methylene compound23 (23°) contradicts the conclusion of Karle et al 22 that addition of a disulfide bridge to the dioxopiperazine ring "does not change appreciably the geometry of the ring". Karle et al came to this conclusion from a comparison of the "fold" in cyc7o-(t.-Pro-L-Leu) and 3,4-dehydroproline anhydride on one hand and several natural epidithiodioxopiperazines on the other hand, compounds which, in our opinion, are not comparable for the conclusion to be drawn, since the disulfide bridge is not the only factor in which they are different from each other.…”

Section: Mementioning

confidence: 82%

Gliotoxin analogs as inhibitors of reverse transcriptase. 2. Resolution and x-ray crystal structure determination

Ottenheijm¹,

Herscheid²,

Tijhuis³

et al. 1978

J. Med. Chem.

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A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to react with the disulfenyl chloride 8 to yield 9 and 10, which were separated by short-column chromatography on silica gel. From these, the optically pure enantiomers 11 and 12, respectively, were obtained by reduction with NaBH4, followed by reoxidation with I2-pyridine. In this way the precursor 7 of the resolving agent could also be recovered. The absolute configurations of 11 and 12 were derived from CD spectra. Kinetic asymmetric transformation of the gliotoxin analogue 2 with the diphosphine 6 gave a 19% enrichment in one enantiomer of the starting material. Surprisingly, both enantiomers were found to inhibit reverse transcriptase, the RNA-dependent DNA polymerase, to the same degree, indicating that there is no relation between this property of epidithiodioxopiperazines and their bridgehead configurations. From the X-ray crystal structure determination it can be seen that there is a considerable torsional and conformational strain in compound 2, which might enhance the ease of cleavage of the S-S bond. A possible relationship between this property and the biological activity of 2 is discussed.

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“…We are aware of only two previously published crystal structure determinations of N-methylated diketopiperazines: cyclo(Sar)2,27a the cyclic dipeptide of A-methylglycine, and Benedetti, Marsh, Goodman 22) 5( 33) 5( 12) 5( 13) 5 (23) 0, 63 822 (24) 112 216 (30) 48 657 ( 22) 732 ( 15) 667 ( 19) 483 ( 14)…”

Section: Resultsmentioning

confidence: 99%

Conformational studies on peptides. X-ray structure determinations of six N-methylated cyclic dipeptides derived from alanine, valine, and phenylalanine

Benedetti¹,

Marsh²,

Goodman³

1976

J. Am. Chem. Soc.

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Conformation and synthesis of diketopiperazines. 3,4-Dehydroproline anhydride

Abstract: On the Conformation and Synthesis of Diketopiperazines.

Cited by 32 publications

References 2 publications

The crystal structure of cyclo-L-prolylglycyl: a refinement of high-angle diffraction data

The crystal structure of cyclo-L-prolylglycyl: a refinement of high-angle diffraction data

Gliotoxin analogs as inhibitors of reverse transcriptase. 2. Resolution and x-ray crystal structure determination

Conformational studies on peptides. X-ray structure determinations of six N-methylated cyclic dipeptides derived from alanine, valine, and phenylalanine

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