Carol P. Huber

Mechanism of hydroxylamine mutagenesis. Crystal structure and conformation of 1,5-dimethyl-N4-hydroxycytosine.

The crystal structure of the title compound, which is a formal analogue of 5-methyl-N4-hydroxycytosine nucleosides, has been determined by X-ray diffraction. The space group is P2(1)/c with a = 7.368 (2), b = 12.096 (3), c = 9.192 (4) A, beta = 113.94 (3) degrees. Three-dimensional intensity data were collected with a four-circle diffractometer, and the structure was refined by block-diagonal least-squares to R = 0.053. The compound is in the imino form, and the exocyclic N4-OH is located essentially in the plane of the pyrimidine ring, and syn to the ring (N(3). There is an intramolecular hydrogen bond involving the N(3)-H as donor and O(4) as acceptor, viz. N(3)-H(31)----O(4)-H. With this conformation, which probably prevails also in solution, the compound would be unable to participate in normal Watson-Crick base pairing. It is shown that a similar situation may prevail for N4-hydroxycytosine nucleosides. The implications with regard to the molecular mechanism of hydroxylamine mutagenesis, with particular reference to the T-even bacteriophages, are discussed. Analogous considerations are applied to an examination of the possible behaviour of hydroxylamine-modified adenine nucleosides.

α-Nucleosides in biological systems: Crystal structure and conformation of α-cytidine

Abstract The structure of α-cytidine, C9H13N3O5, monoclinic with space group C2 and cell parameters a = 20.064 (3) A , b = 7.100 (1) A , c = 7.860 (2) A , β = 104.60 (2)°, Z = 4, was determined by X-ray diffraction using a combination of direct methods, Patterson and difference Fourier techniques and refined by block-diagonal least-squares to a final R of 0.033 for 1002 reflections measured on a diffractometer. The glycosidic torsional angle, χCN = −28.4°, is in the anti region; the sugar pucker is C(2′)exo-C(3′)endo in a nearly pure 32H twist; and the conformation of C(4′)-C(5′) is gauche-gauche. The molecules are bound by hydrogen bonds in the lattice with little likelihood of base-stacking interactions. The molecular features of the compound are compared and contrasted with those of its naturally occurring β-anomer, and some biological implications of this structure, and α-nucleosides in general, are discussed.

Approaches to the total synthesis of triterpenes. VIII. The ABC + D/E approach. Synthesis and X-ray structure determination of 1β,4a β-dimethyl-7-methoxy-1α- (7′,7′-ethyleneketal-6′,6′-dimethyl-3′-ketooctyl)-3,4,4a,9,10,10aα-hexahydro- 2(l-H)phenanthrone

The title compound was made following a projected synthetic route to pentacyclic triterpenes. The key step in the route is the alkylative trapping of the enolate derived from the enol trimethylsilyl ether 8. The stereochemical consequence of this reaction is confirmed by a single crystal X-ray structure determination on 4, which although of no further utility in the projected synthesis, nevertheless served as a useful template for this determination. In this way, ongoing work in a parallel series of compounds rests on a firm stereochemical footing.

Structure and properties of a trans–anti photodimer of 5-methylorotate

5-Methylorotate is relatively radiation resistant in aqueous fluid medium, but readily photodimerizes in an ice matrix. Rapid formation of such a matrix made possible the preparative isolation of the photodimer in good yield. The potassium salt of the photodimer crystallizes as the hexahydrate, C12H10N4O8K2•6H2O. The crystals are triclinic with space group a = 8.139(3), b = 9.759(3), c = 7.398(3) A, a = 100.28(7), β = 74.22(5), γ = 108.67(7)°, and V = 533.0 A3, Z = 1. The structure was solved by Patterson and direct methods; refinement by block-diagonal least-squares converged at R = 0.041 for all 1671 observed reflections. The pyrimidine rings of the centrosymmetric photodimer are arranged in trans–anti configuration across the planar cyclobutane ring. The potassium ion is seven-coordinated. In aqueous medium the photodimer exhibits a pKa of 12.8 due to dissociation of the ring N(3) hydrogen. Irradiation in aqueous medium at 254 nm leads to quantitative regeneration of the monomer with a quantum yield of...

Sesquiterpenoid stress compounds of Datura stramonium: biosynthesis of the three major metabolites from [1,2-13C]acetate and the X-ray structure of 3-hydroxylubimin

2,3-Germacrenediol, lubimin, and hydroxylubimin, the major stress metabolites of Datura stramonium, incorporate sodium [1,2-13C]acetate in patterns, as shown by 13C n.m.r. spectroscopy, which establish their structures and mevalonate origins; the X-ray structure of hydroxylubimin completely defines its stereochemistry.

Approaches to the synthesis of triterpenoids—VII

Abstract The synthesis and X-ray crystal structure determination of 8-methoxy-3,3,10bα, 12aβ-tetramethyl-1,2,5,6,10b,1 1,12,12a-octahydro-4(3H)-chrysenone is described. This and related compounds represent useful intermediates for pentacyclic triterpene synthesis.

Approaches to the synthesis of triterpenoids—VII: The synthesis of some reduced chrysene derivatives as suitable intermediates for pentacyclic triterpenes. Synthesis via BCDE ring construction

Abstract The synthesis and X-ray crystal structure determination of 8-methoxy-3,3,10bα, 12aβ-tetramethyl-1,2,5,6,10b,1 1,12,12a-octahydro-4(3H)-chrysenone is described. This and related compounds represent useful intermediates for pentacyclic triterpene synthesis.

APPROACHES TO THE TOTAL SYNTHESIS OF TRITERPENES. VIII. THE ABC + D/E APPROACH. SYNTHESIS AND X‐RAY STRUCTURE DETERMINATION OF 1β,4Aβ‐DIMETHYL‐7‐METHOXY‐1α‐((7,7‐ETHYLENEDIOXY)‐6,6‐DIMETHYL‐# 3‐OXOOCTYL)‐3,4,4A,9,10,10Aα‐HEXAHYDRO‐2(1H)‐PHENANTHRONE

The title compound was made following a projected synthetic route to pentacyclic triterpenes. The key step in the route is the alkylative trapping of the enolate derived from the enol trimethylsilyl ether 8. The stereochemical consequence of this reaction is confirmed by a single crystal X-ray structure determination on 4, which although of no further utility in the projected synthesis, nevertheless served as a useful template for this determination. In this way, ongoing work in a parallel series of compounds rests on a firm stereochemical footing.