Synthesis of a 6,6-spiroketal amino acid and its incorporation into a peptide turn sequence using solid-phase peptide synthesis.

Spiropins for SPPS: The rigid structure of an anomerically stabilised spiroketal motif enables the appendage of substituents in a fixed conformation. To assess the ability of a spiroketal motif to induce a turn structure and participate in solid-phase peptide synthesis (SPPS), an Fmoc-spiroketal amino acid was synthesised and incorporated into a spiroketal-containing cyclic peptide.

Enantioselective synthesis of C-linked spiroacetal-triazoles as privileged natural product-like scaffolds.

The enantioselective synthesis of novel C-linked spiroacetal-triazoles 10 is reported. The key step involves reaction of acetylenic spiroacetal 11 with several azides by the Copper-Catalysed Azide-Alkyne Cycloaddition (CuAAC). The biologically privileged spiroacetal scaffold 11 was prepared from silyl-protected Weinreb amide 19 using several reliable Grignard additions and a highly diastereoselective enzymatic kinetic resolution.

Synthesis of spiroacetal-nucleosides as privileged natural product-like scaffolds.

The elaboration of a 6,6-spiroacetal scaffold to incorporate a nucleoside unit at the anomeric position is described. The novel spiroacetal-nucleoside hybrids were generated via nucleosidation of acetoxy-spiroacetal with a series of silylated nucleobases under Vorbrüggen conditions.

Synthesis of spiroacetal-triazoles as privileged natural product-like scaffolds using "click chemistry".

The elaboration of a 6,6-spiroacetal scaffold to incorporate a triazole unit as a peptide bond surrogate at the anomeric position is described. The novel spiroacetal-triazole hybrid structures were generated via cycloaddition of a spiroacetal azide to a series of alkynes. The spiroacetal framework was constructed via Barbier reaction of bromide 10 with Weinreb amide 11, followed by acid-catalysed deprotection and cyclisation to afford the 6,6-spiroacetal ring system. The resultant ethoxy-spiroacetal 8 was converted to spiroacetal azide 5, which was then elaborated into a series of spiroacetal-triazole derivatives 7.

3-Allyl-2-hydr-oxy-5,6,8-trimethoxy-naphthalene-1,4-dione.

In the crystal structure of the title compound, C(16)H(16)O(6), a pair of naphthoquinone rings are linked via O-H⋯O-C hydrogen bonds in a nearly orthogonal arrangement. This dimeric unit is linked to a neighbouring dimer by π-π stacking inter-actions between the naphthoquinone rings, where the distance between the mean plane of the naphtoquinone backbones is 3.468 Å, and O-H⋯O-C hydrogen bonds.

(±)-N-(3-Hydr-oxy-1,2-diphenyl-prop-yl)-4-methyl-benzene-sulfonamide.

In the title compound, C(22)H(23)NO(3)S, the relative stereochemistry of the two stereogenic centres is anti with respect to the H atoms. The mol-ecular packing of the crystal shows a double-strand arrangement, consisting of one strand of (S*,S*) enanti-omers and one strand of (R*,R*) enanti-omers. Both strands lie parallel to each other along the a axis. Each strand is made up of dimers in which the mol-ecules are connected to each other via an inter-molecular O-H⋯O hydrogen bond between the hydroxyl groups and an O-H⋯π inter-action with the aromatic ring. These units are then connected to neighbouring dimers via N-H⋯O hydrogen bonds and C-H⋯O interactions. Intramolecular C-H⋯O interactions are also observed.

(±)-1-{8'-(tert-Butyl-diphenyl-silyloxy-meth-yl)-1',7'-dioxaspiro-[5.5]undecan-2'-yl}uridine.

The crystal structure of the title compound, C(30)H(38)N(2)O(5)Si, has been investigated to establish the relative stereochemistry at the spiro ring junction and the two anomeric centres. Each of the O atoms in the tetra-hydro-pyran rings adopts an axial position on the neighbouring ring. This bis--diaxial conformation is adopted, thus gaining maximum stablization from the anomeric effect. The silyl-protected hydroxy-methyl and uracil substituents adopt equatorial positions on their associated tetra-hydro-pyran rings, thereby minimizing unfavourable steric inter-actions. The dimeric (2'R*,6'R*,8'R*)- and (2'S*,6'S*,8'S*)-uridine units are connected to each other across crystallographic inversion centres via inter-molecular N-H⋯O hydrogen bonds.

(1R,1'R,3S,3'S)-5,5',10,10'-Tetra-meth-oxy-1,1',3,3'-tetra-methyl-3,3',4,4'-tetra-hydro-1H,1'H-8,8'-bi[benzo[g]isochromene].

In the title compound, C(34)H(38)O(6), the methyl groups on each pyran ring exhibit 1,3-cis stereochemistry, established during synthesis by pseudo-axial delivery of hydride during a lactol reduction step. In the crystal structure, the mol-ecule lies on a twofold rotation axis and the torsion angle about the central diaryl bond is 41.3 (1)°. The mol-ecules pack in a herringbone arrangement.

(1R,6R)-1-Methyl-8-aza-spiro-[5.6]dodecan-7-one.

The crystal structure of the title compound, C(12)H(21)NO, has been investigated to establish the absolute stereochemistry at position 1. The absolute stereochemistry at the quaternary centre at position 6 is established to be R using an asymmetric Birch reductive alkyl-ation reaction for which the stereochemical outcome is known. The crystal structure indicates the presence of two conformers of the bicyclic (1R,6R)-spiro-lactam ring system that differ in the conformation adopted by the six-membered ring. In one conformer, the meth-yl group adopts an axial position whereas in the other conformer, the same methyl group adopts an equatorial position. In both conformers, the seven-membered ring adopts a chair conformation. The two conformers of the bicyclic spiro-lactam are connected to each other via inter-molecular N-H⋯O hydrogen bonds forming a heterodimer. The asymmetric unit contains two such dimers.

(±)-2'-Phenyl-cyclo-hexa-nespiro-4'-(aze-pano[1,2-b]isoxazolidine).

In the crystal structure of the racemic title isoxazolidine, C(19)H(27)NO, the relative stereochemistry between the phenyl group and the bridgehead H atom is shown to be syn. There are two mol-ecules in the asymmetric unit, one of which is the 7R*,13R* enanti-omer, and one of which is the 7S*,13S* enanti-omer. These enanti-omers adopt different orientations of the phenyl ring with respect to the isoxazolidine ring, with C-C-C-C torsion angles of 63.6 (4) and 86.8 (4)°, respectively. In both enanti-omers, the six-membered ring adopts a chair conformation, while the seven-membered ring adopts a twist-chair conformation.

(±)-Cyclo-hexane-1,2-diyl bis-(4-nitro-benzoate).

The crystal structure of the title compound, C(20)H(18)N(2)O(8), has been investigated to establish the relative stereochemistry between the ester groups. The cyclo-hexane ring adopts a chair conformation, in which the two ester groups occupy the adjacent equatorial positions in a trans relationship with each other. The mol-ecules assemble in the crystal as chains along the c axis via C-H⋯π inter-actions between the cyclo-hexane ring and a pair of nitro-phenyl rings of the neighbouring mol-ecule. Also observed are π-π stacking inter-actions between the nitro-phenyl rings of neighbouring chains, with a perpendicular distance between these rings of 3.409 Šand a slippage of 0.969 Å.