First and unexpected synthesis of macrocyclic cyclophane-based unusual α-amino acid derivatives by phosphazene base without high dilution conditions

First synthesis of a macrocylic cyclophane-based unusual α-amino acid derivative 11 by coupling of ethyl isocyanoacetate with 1,2-bis(4-bromomethylphenyl)ethane under phase-transfer catalysis (PTC) conditions. Phosphazene base such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) is useful to improve the yield of cyclophane derivative without high dilution conditions.© Elsevie

Synthesis of two new hexaquinanes: advanced C20 precursors to dodecahedrane

A simple synthesis of hexaquinane diones 2 and 22 involving bench-top chemicals is reported. These two hexaquinanes are advanced C20 precursors to dodecahedrane 1 either by C-C bond formation reactions or by the isomerisation approach.© Elsevie

Optimization of interactions in crystal packing revealed by crystal structures [ethyl 2-(formylamino)-3-thien-2-yl-2-(thien-2-ylmethyl)propanoate and ethyl 3-(5-bromothien-2-yl)-2-[(5-bromothien-2-yl)methyl]-2-(formylamino)propanoate]

The title compounds, C15H14NO3S2 (I) and C15H15Br2NO3S2 (II), are derivatives of Aib (α-aminoisobutyric acid) with thiophene rings substituted at the Cα position. The Cα substitution causes the backbone to assume an extended conformation in the crystal structure. N–H and C–H donors share the thiophene ring π system for X–H...π interactions. The packings of the molecules are stabilized by intermolecular N–H...O, C–H...O, C–H...π and C–H...Br hydrogen bonds. Br...O interactions and a weak dihydrogen bond have also been observed in the crystal structure of II. The packing adopted by II has maximized the number of interactions that are possible.© Elsevie

Ethyl 2-form­amido-2-(4-iodo­benzyl)-3-(4-iodo­phenyl)­propionate and ethyl 2-(3-bromo­benzyl)-3-(3-bromo­phenyl)-2-form­amidopropionate

The title compounds, C<SUB>19</SUB>H<SUB>19</SUB>I<SUB>2</SUB>NO<SUB>3</SUB> and C<SUB>19</SUB>H<SUB>19</SUB>Br<SUB>2</SUB>NO<SUB>3</SUB>, are derivatives of &#945;-amino­isobutyric acid with halogen substituents at the para and meta positions, respectively. The ethoxycarbonyl and formamide side chains attached to the C<SUB>&#945;</SUB> atom of the mol­ecule adopt extended and folded conformations, respectively. The crystal structures are stabilized by N-H&#183;&#183;&#183;O, C-H&#183;&#183;&#183;O, C-Br&#183;&#183;&#183;O and C-I&#183;&#183;&#183;O interactions

Precursors to dodecahedrane

The title compounds, (2R,2''S,3b'S,4a'R,7b'S,8a'R)-per­hydro­di­spiro­[furan-2,3'-di­cyclo­penta­[a,e]­pentalene-7',2''-furan]-5,5''-dione, C<SUB>20</SUB>H<SUB>26</SUB>O<SUB>4</SUB>, and (3aR,3bR,4aR,4bS,5aS,8aR,8bR,9aR,9bS,10aS)-per­hydro­dipentaleno­[2,1-a:2',1'-e]­pentalene-1,6-dione, C<SUB>20</SUB>H<SUB>26</SUB>O<SUB>2</SUB>, are intermediates identified during the synthesis of dodecahedrane. Crystallographic studies have established the ring-junction stereochemistry for these important intermediates. All the ring junctions are cis-fused, and the molecular packing is stabilized by van der Waals interactions

Cyclooxygenase-2: an attractive target for fruitful drug design

Cyclooxygenase, an enzyme involved in the conversion of C-20 acids to prostaglandins, exists in two isoforms. A third isoform has been recently encountered. COX-1 is constitutively expressed and has a gastroprotective function. COX-2, induced at the site of injury, is responsible for the expression of pro-inflammatory prostaglandins. Despite overall similarities, COX-1 and COX-2 show subtle differences in amino acid composition at the active sites. COX-2 has valine at positions 89 and 523, while COX-1 has isoleucine, resulting in larger space availability in the former. Further, the presence of valine at position 434 in COX-2 as against isoleucine in COX-1 allows a gate mechanism to operate in favour of the former. Molecular modelling studies explain the preferential COX-2 inhibitory activity of some nonsteroidal anti-inflammatory agents like celecoxib (3), rofecoxib (4), nimesulide (5), meloxicam (6), nabumetone (10) and etodolac (13) in terms of binding, destabilizing and intermolecular energies. A few modified meloxicam derivatives like 19 and 20 are likely to have superior COX-2 selectivity

Conformational switching caused by bi­phenyl substitution at the C<SUP>&#945;</SUP> position: ethyl 2-benzyl-2-(formyl­amino)-3-phenyl­propionate and ethyl 3-(1,1'-bi­phenyl-4-yl)-2-(formyl­amino)-2-(4-phenyl­benzyl)­propionate

The title compounds, C19H21NO3 and C31H29NO3, are derivatives of &#945;-aminoisobutyric acid, with benzyl and di­benzyl substitution. The pseudo-peptide formed by the N-formyl and ethyl ester substitution at the C&#945; position switches from a trans-trans to a trans-cis configuration as a result of bi­phenyl substitution. The packing of the compounds is stabilized by N-H&#183;&#183;&#183;O and C-H&#183;&#183;&#183;O hydrogen bonds

Ethyl 6-acetylamino-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylate

The title compound, C<SUB>20</SUB>H<SUB>21</SUB>NO<SUB>3</SUB>, is a derivative of Aib (α-aminoisobutyric acid) and is cyclized at the C<SUP>α</SUP> position by bi-phenyl rings. The seven-membered ring possesses C2 symmetry. The C<SUP>α</SUP> cyclization causes the backbone to assume a helical conformation in the crystal structure. The packing of the mol-ecules is stabilized by intermolecular C-H···O, C-H···π and N-H···O hydrogen bonds

Structure of YqgQ protein from Bacillus subtilis, a conserved hypothetical protein

The crystal structure of the hypothetical protein YqgQ from B. subtilis is reported at 2.1 Å resolution