Formal total synthesis of 2-pupukeanone via radical mediated cyclisation of an enyne

Diels-Alder reaction of the dienone 12, obtained by C-alkylation of sodium 2,6-dimethylphenoxide, with acrylonitrile and phenyl vinyl sulfones generate the enynes 14 and 17. Tributyltin radical addition to the terminal acetylene in 14 and 17 lead to the vinylstannanes 15 and 18 via 5-exo trig cyclisation of the resulting vinyl radical, which on oxidative cleavage furnishes the isotwistane-diones 16 and 19. Reductive desulfonylation of the diketosulfone 19 furnishes the dione 11, constituting a formal total synthesis of 2-pupukeanone 5 and 2-isocyanopupukeanone 3.

Xylan-Degrading Enzymes from the Thermophilic Fungus Humicola Zanuginosa (Griffon and Maublanc) Bunce: Action Pattern of Xylanase and beta-Glucosidase on Xylans, Xylooligomers and Arabinoxylooligomers

The mode of action of xylanase and beta-glucosidase purified from the culture filtrate of Humicola lanuginosa (Griffon and Maublanc) Bunce on the xylan extracted from sugarcane bagasse and on two commercially available larchwood and oat spelt xylans, on xylooligomers and on arabinoxylooligomers was studied. While larchwood and oat spelt xylans were hydrolyzed to the same extent in 24 h, sugarcane bagasse xylan was hydrolyzed to a lesser extent in the same period. It was found that the rate of hydrolysis of xylooligomers by xylanase increased with increase in chain length, while beta-glucosidase acted rather slowly on all the oligomers tested. Xylanase exhibited predominant ''endo'' action on xylooligomers attacking the xylan chain at random while beta-glucosidase had ''exo'' action, releasing one xylose residue at a time. On arabinoxylooligomers, however, xylanase exhibited ''exo'' action. Thus, it appears that the presence of the arabinose substituent has, in some way, rendered the terminal xylose-xylose linkage more susceptible to xylanase action. It was also observed that even after extensive hydrolysis with both the enzymes, substantial amounts of the parent arabinoxylooligomer remained unhydrolyzed together with the accumulation of arabinoxylobiose. It can therefore be concluded that the presence of the arabinose substituent in the xylan chain results in linkages that offer resistance to both xylanase and beta-glucosidase action.

Acid-catalysed cyclisations: structures of novel products isolated in the reaction of 2-[3-(2,6-dimethoxyphenyl)but-2-enyl]-2-methylcyclopentane-1,3-dione with MeOH-HCl

Reaction of the title compound (1a) with anhydrous MeOH-HCl gave 2-endo-(2,6-dimethoxyphenyl)-2-exo-methyl-5-methylbicyclo[3.2.1]octane-6,8-dione (3a), 1,5,14-timethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),9(11)-tetraen-17-one (4), 1,5-dimethoxy-5,8-seco-6,7-dinorestra-1,3,5(10),8,14-pentaen-17-one (5), and 3,4,5,6-tetrahydro-2,7-dimethoxy-3,6-dimethyl-3,2,6-(13-oxopropan[1]yI[3]ylidene)-2H-1-benzoxocin (6). Structures assigned to compounds (3a), (4), and (6) are based on spectral data. The exo-tricyclic acetal structure (6) was further confirmed by the analysis of the 1H n.m.r. spectra of the isomeric alcohols (11) and (12), obtained by sodium borohydride reduction of (6).

Structure of 5'-O-acetyl-2',3'-O-isopropylideneuridine, C14H18N2O7

M r = 326.3, monoclinic, P21, a --= 6.510 (2), b=8.432 (2), c= 15.114 (2),a, /~= 101.42 (3) ° , Z = 2, V= 813.15 A 3, D x = 1-33 Mg m -3, F(000) = 172, 2(Cu Ka) = 1.5418/~,, g(Cu Ka) = 0.906 mm -~, final R = 6.4% for 1924 observed counter reflections. The conformation about the glycosidic bond is syn [torsion angle C(6)-N(1)-C(1')-O(4')=-103.9(3)°]. The sugar pucker is C(2')-exo,C(3')-endo (3Tz). The conformation about the C(4')-C(5') bond is gauche-trans. An uncommon intermolecular hydrogen bond involving the ribose-ring oxygen O(1') and the base-nitrogen N(3) stabilizes the crystal structure.

Conformational analysis of hydroxyproline and its protected derivatives by 1H NMR

From a computer simulation of the 270 MHz 1H NMR spectra of hydroxyproline (Hyp) and its protected derivatives, precise values of ring vicinal coupling constants were obtained. These couplings were related to ring torsional angles, using a Karplus type analysis. From the NMR analysis it was observed that the pyrrolidine ring possesses a unique and highly homogeneous conformation (Cγ-exo form). Temperature dependence studies on protected dipeptides suggest that the pyrrolidine ring conformation is independent of backbone conformation. An unusual X-Hyp, β-turn was observed for Boc-Aib-Hyp-NHMe.

Structure Of 5'-Deoxy-5',6-Epithio-5,6-Dihydro-2',3'-O-Isopropylideneuridine, C12h16n2o5s

Mr=300.33 , triclinic, P1, a=5.635 (2), b=11.077(2), c=11.582(2)A, a= 70.48 (1), fl= 88.16 (3), y=80.56(3) ° , V= 670.325 A3, Z=2, D x = 1.49 Mg m -3, Cu Ka, n= 1.54184 ,A, g = 2.308mm -1, F(000)=316, T=301K, R=0.054, R w = 0.093 for 1944 observed counter reflections. The sulphur position with respect to the dihydrouracil ring, which is of possible relevance to the action of thymidylate synthetase, is axial in molecule A and equatorial in B. Both molecules show the anti conformation about the glycosidic bond [torsion angle C(6)-N(1)-C(1')-O(4'), 2'CN = 21.6 (9) and 29.4 (10) °] and have the C(4')-endo, O(4')-exo (40T) sugar conformation. The dioxolane-ring conformation is O(2')-endo in A and C(7)-endo in B. The dihydrouracil rings show self base pairing with hydrogen bondsN(3A)...O(ZB) and N(3B)...O(ZA).

Structure of a thionucleoside: 5'-deoxy-5',6-epithio-5,6-dihydro-2',3'-O-isopropylidene-3-methyluridine

C13HlsN205 S, M r = 314.35, orthorhombic, P212121 with a = 39.526 (4), b = 6.607 (2), c = 5.661 (2) A, Z = 4, V = 1478.36 A 3, D c = 1.412 Mg m -3, Cu Ka radiation. Final R = 0.073 for 1154 observed counter reflections. The sulphur atom is in a pseudo-equatorial position with respect to the dihydrouracil ring. The sugar pucker is predominantly O(l')-exo unlike the C(3')-exo,C(4')-endo observed for 2',3'-O-isopropylideneuridine (ISPU). The fivemembered dioxolane ring has C(7) displaced by 0.497 (7)A from the best plane through atoms 0(2'), C(2'), C(3'), 0(3'), in contrast to ISPU where 0(3') shows the maximum deviation.

Structure of 5-Bromo-2',3'-O-isopropylideneuridine, C12H15BrN206

Mr= 363.17, orthorhombic, P21212 ~, a= 5.251(4), b=14.962(5), c=19.112(5)A, U= 1501.41/k 3, Z=4, Dx=1.61Mgm -3, /t(CuKa)= 3.02 mm -1, 2(Cu Ka)= 1.5418/~, final R = 7.0% for 1091 reflections with Fo> 2e(Fo). The glycosidic torsion angle ZCN is 13"1 (12) °. The ribose has a C (3')-exo,C (4)-endo twist geometry. The dioxolane ring assumes an envelope conformation with 0(3') displaced by 0.453 (10)/k from the plane of the other four atoms. The conformation about the C(4')-C(5') bond is gauche-gauche. The structure is stabilized by two hydrogen bonds between screw-axis-related molecules. The crystal packing and the conformation of the molecule are very similar to those found in the structure of 2',3'-O-isopropylideneuridine which lacks the Br atom at the 5-position.

Structure of Disodium Deoxyeytidine 5'-Phosphate Heptahydrate, C9H 12N30TP2-.2N a +. 7H 20

M,=477.3, orthorhombic, P2~2~2~, a= 6.719.(4), b=29.614(15), c= 9.559 (3) ~, Z=4, U-- 1902.0 A 3, D x = 1.67 Mg m -3, 2(Cu Ka) = 1.5418A, /~=l.90mm -1, T=290K. Final R for 1809 observed reflections is 0.045. The structure shows an unusual gauche-trans conformation about the C(4')-C(5') bond, while the sugar pucker [C(3')-exo] and glycosidic torsion angle [)CCN = 70.2 (5) °, anti] are normal. The two Na + ions do not interact with the molecule directly, being completely surrounded by water molecules. The cytosine bases are stacked, with a separation distance of 3.36 (5) A.

Structure of 2-(2,6-dimethoxyphenyl)-2,5- dimethylbicyclo[3.2.1]octane-6,8-dione

C18H2204, orthorhombic, P212~21, a = 7.343 (4), b = 11.251 (4), c = 19.357 (4)A, Z = 4, Dr, ' = 1.20, D e = 1.254 g cm -3, F(000) = 648, p(MoKa) = 0.94 cm -~. X-ray intensity data were collected on a Nonius CAD-4 diffractometer and the structure was solved by direct methods. Full-matrix least-squares refinement gave R = 0.052 (R w = 0.045) for 1053 observed reflections. The stereochemical configuration at C(2) has been shown to be 2-exo-methyl-2-endo-(2,6-dimethoxyphenyl), i.e. (3) in contrast to the structure (2) assigned earlier based on its ~H NMR data.

Structure Of A Thionucleoside - 5'-Deoxy-5',6-Epithio-5,6-Dihydro-2',3'-Ortho-Isopropylidene-3-Methyluridine

C13HlsN205 S, M r = 314.35, orthorhombic, P212121 with a = 39.526 (4), b = 6.607 (2), c = 5.661 (2) A, Z = 4, V = 1478.36 A 3, D c = 1.412 Mg m -3, Cu Ka radiation. Final R = 0.073 for 1154 observed counter reflections. The sulphur atom is in a pseudo-equatorial position with respect to the dihydrouracil ring. The sugar pucker is predominantly O(l')-exo unlike the C(3')-exo,C(4')-endo observed for 2',3' O-isopropylideneuridine (ISPU). The fivemembered dioxolane ring has C(7) displaced by 0.497 (7)A from the best plane through atoms 0(2'), C(2'), C(3'), 0(3'), in contrast to ISPU where 0(3') shows the maximum deviation.

The Structure Of 2',3'-O-Isopropylideneuridine

C12HI6N206 is orthorhombic, P2x2121, with a = 19.890 (5), b = 12.789 (2), c = 5.236 (1) A, Z = 4, U = 1331.9/~ 3, F(000) = 600. Mo Ka (/~ = 0.123 mm -1) intensities for 940 unique reflections up to sin 0/2 = 0.538/k -1 were collected on a CAD-4 diffractometer. Final R = 0.034. The glycosidic torsion angle 2~CN is 3"4 °, significantly smaller than that (56.5 °) in 2',3'- -methoxymethyleneuridine (MMU). The ribose moiety has a C(3')-exo-C(4')-endo twist conformation, in contrast to the C(2')-endo conformation in MMU. However, the maximum amplitudes of pucker for the ribose and dioxolane rings are very nearly the same for the two structures. The conformation about C(4')-C(5') is gauche-gauche (~0oo = -68-4, Ooc = 51.3°).

Structures of isopropylidene nucleoside derivatives - implications for ribose ring flexibility under external cyclic constraints

Crystal structures of six isopropylidene nucleoside derivatives are described. The results show that, under external cyclic constraints, the ribose assumes a variety of unusual conformations. In those compounds which possess a base-to-sugar cyclization through the C(4′) atom, the furanose pucker is predominantly C(4′)-endo, O(4′)-exo. The possible relevance of the sulphur geometry in two of the compounds to certain structural aspects of the action of the enzyme thymidylate synthetase is also pointed out.

The Crystal Structure of Pivaloyl- D- prolyl-L- prolyl- L-alanyl-N- methylamide

Pivaloyl-D-prolyl-L-prolyl-L-analyl-N-methylam~de (I), C1UH32N40c4r,y stallizes in the orthorhombic space group P21212,w ith four molecules in a unit cell of dimensions a = 9.982 (l),b = 10.183 (3), c = 20.746 (2)A . The structure has been refined to R 0.048 for 1 745 observed reflections. All the peptide bonds in the molecule are trans and both the prolyl residues are in the CY-exo-conformation. The molecule assumes a highly folded conformation in which a Type II' DL bend is followed by a Type I LL bend, both stabilised by intramolecular 4 + 1 hydrogen bonds. This conformation, which has been observed for the first time, is of interest in relation to the structure of gramicidin S.

Structure of 2-(2,6-Dimethoxyphenyl)-2,5-dimethylbicyclo[3.2. l]octane-6,8-dione

C18H2204, orthorhombic, P212~21, a = 7.343 (4), b = 11.251 (4), c = 19.357 (4)A, Z = 4, Dr, ' = 1.20, D e = 1.254 g cm -3, F(000) = 648, p(Mo Ka) = 0.94 cm -~. X-ray intensity data were collected on a Nonius CAD-4 diffractometer and the structure was solved by direct methods. Full-matrix least-squares refinement gave R = 0.052 (R w = 0.045) for 1053 observed reflections. The stereochemical configuration at C(2) has been shown to be 2-exo-methyl-2-endo- (2,6-dimethoxyphenyl), i.e. (3) in contrast to the structure (2) assigned earlier based on its ~H NMR data.