Organic & Biomolecular Chemistry (v.12, #13)

Front cover (1997-1998).

Contents list (1999-2004).

Gold nanoparticle (AuNPs) and gold nanopore (AuNPore) catalysts in organic synthesis by Balaram S. Takale; Ming Bao; Yoshinori Yamamoto (2005-2027).
Organic synthesis using gold has gained tremendous attention in last few years, especially heterogeneous gold catalysis based on gold nanoparticles has made its place in almost all organic reactions, because of the robust and green nature of gold catalysts. In this context, gold nanopore (AuNPore) with a 3D metal framework is giving a new dimension to heterogeneous gold catalysts. Interestingly, AuNPore chemistry is proving better than gold nanoparticles based chemistry. In this review, along with recent advances, major discoveries in heterogeneous gold catalysis are discussed.

A novel methodology for synthesis of dihydropyrazole derivatives as potential anticancer agents by Xu Wang; Ying-ming Pan; Xiao-chao Huang; Zhong-yuan Mao; Heng-shan Wang (2028-2032).
A novel, simple, and efficient method for the synthesis of 4,5-dihydropyrazole derivatives has been developed. The reaction proceeded through the base-induced isomerization of easily accessible propargyl alcohols followed by cyclization of α,β-unsaturated hydrazones. Furthermore, selected compounds 3ab and 3ac exhibited good activities against Bel-7404 (human hepatoma cancer), HepG2 (human liver cancer), NCI-H460 (human lung cancer) and SKOV3 (human ovarian cancer) cell lines with IC50 in the range of 22–46 μmol L−1.

Fluorescent probes for detecting monoamine oxidase activity and cell imaging by Xuefeng Li; Huatang Zhang; Yusheng Xie; Yi Hu; Hongyan Sun; Qing Zhu (2033-2036).
A series of new fluorogenic probes for monoamine oxidases (MAOs) were reported based on an oxidation and β-elimination mechanism. The limits of detection of the probes for MAO-A and -B were determined to be 3.5 and 6.0 μg mL−1 respectively. These probes displayed strong activity towards MAOs, especially MAO-B. Cellular imaging studies were also successfully conducted with MCF-7 cells.

Direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis by Zhu-Jia Feng; Jun Xuan; Xu-Dong Xia; Wei Ding; Wei Guo; Jia-Rong Chen; You-Quan Zou; Liang-Qiu Lu; Wen-Jing Xiao (2037-2040).
Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50–91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

The development of an Ir-catalyzed ortho-C–H borylation of aromatic aldimines derived from pentafluoroaniline is reported. This reaction proceeded at 120 °C to afford the corresponding borylated products in high yield with good regioselectivity using an Ir complex formed in situ from [Ir(OMe)(cod)]2/2(C6F5)3P in the presence of 2-norbornene.

Encapsulation and selectivity of sulfate with a furan-based hexaazamacrocyclic receptor in water by Md Mhahabubur Rhaman; Lucky Ahmed; Jing Wang; Douglas R. Powell; Jerzy Leszczynski; Md. Alamgir Hossain (2045-2048).
A furan-based hexaazamacrocycle encapsulates a sulfate anion in its cavity showing strong affinity and selectivity for sulfate in water over a wide range of inorganic anions. The DFT calculations demonstrate that the receptor provides binding sites as hydrogen bonding donors and electrostatic positive charges for the strong binding of sulfate.

A carboxy-directed asymmetric hydrogenation of α-alkyl-α-aryl terminal olefins was developed by using a chiral spiro iridium catalyst, providing a highly efficient approach to the compounds with a chiral benzylmethyl center. The carboxy-directed hydrogenation prohibited the isomerization of the terminal olefins, and realized the chemoselective hydrogenation of various dienes. The concise enantioselective syntheses of (S)-curcudiol and (S)-curcumene were achieved by using this catalytic asymmetric hydrogenation as a key step.

Comparative analysis of cross strand aromatic–Phe interactions in designed peptide β-hairpins by Kamlesh Madhusudan Makwana; Radhakrishnan Mahalakshmi (2053-2061).
The mode(s), geometry and strength of interaction of the three aromatic amino acids, namely Phe, Tyr and Trp, with the benzyl side chain of Phe, at the non-hydrogen bonding position of designed model octapeptide β-hairpins, nucleated by the central DPro–Gly turn, have been examined. In the absence of solvent-driven hydrophobic forces, the extent of contribution of such interactions indicates that the stereospecific face-to-edge (FtE) geometry of aromatic rings is most stabilizing in the Trp–Phe pair. In contrast, our study shows that the Tyr–Phe pair exhibits the weakest interaction energy, despite its abundance in protein structures. The contribution of aromatic interactions as opposed to the influence of spatial proximity to electron-rich groups, to the observed anomalous backbone and side chain chemical shifts, has also been delineated. Our findings indicate that the Trp–Phe pair contributes an additional ∼0.9 kcal mol−1 and ∼1.3 kcal mol−1 towards scaffold stabilization, when compared with the Phe–Phe and Tyr–Phe pair, respectively, even in an amphipathic solvent such as methanol. Detailed NMR analysis of backbone resonances, as well as the extent of pronounced anomalous chemical shifts, indicates that the strength of aromatic interactions with Phe follows the order Trp > Phe > Tyr. Furthermore, the advantages of Trp–Phe or Phe–Phe pairs as alternative structure stabilizing elements are also highlighted.

Making Fe(BPBP)-catalyzed C–H and CC oxidations more affordable by Vital A. Yazerski; Peter Spannring; David Gatineau; Charlotte H. M. Woerde; Sara M. Wieclawska; Martin Lutz; Henk Kleijn; Robertus J. M. Klein Gebbink (2062-2070).
The limited availability of catalytic reaction components may represent a major hurdle for the practical application of many catalytic procedures in organic synthesis. In this work, we demonstrate that the mixture of isomeric iron complexes [Fe(OTf)2(mix-BPBP)] (mix-1), composed of Λ-α-[Fe(OTf)2(S,S-BPBP)] (S,S-1), Δ-α-[Fe(OTf)2(R,R-BPBP)] (R,R-1) and Δ/Λ-β-[Fe(OTf)2(R,S-BPBP)] (R,S-1), is a practical catalyst for the preparative oxidation of various aliphatic compounds including model hydrocarbons and optically pure natural products using hydrogen peroxide as an oxidant. Among the species present in mix-1, S,S-1 and R,R-1 are catalytically active, act independently and represent ca. 75% of mix-1. The remaining 25% of mix-1 is represented by mesomeric R,S-1 which nominally plays a spectator role in both C–H and CC bond oxidation reactions. Overall, this mixture of iron complexes displays the same catalytic profile as its enantiopure components that have been previously used separately in sp3 C–H oxidations. In contrast to them, mix-1 is readily available on a multi-gram scale via two high yielding steps from crude dl/meso-2,2′-bipyrrolidine. Next to its use in C–H oxidation, mix-1 is active in chemospecific epoxidation reactions, which has allowed us to develop a practical catalytic protocol for the synthesis of epoxides.

The first convergent total synthesis of penarolide sulfate A2, a novel α-glucosidase inhibitor by Yangguang Gao; Qiuli Shan; Jun Liu; Linlin Wang; Yuguo Du (2071-2079).
Penarolide sulfate A2, a 31-membered macrolide encompassing a proline residue and three sulfate groups, was firstly synthesized in 16 linear steps with 4.8% overall yield. Three consecutive stereogenic centers in penarolide sulfate A2 were efficiently derived from natural chiral template l-arabinose. The crucial assembly reactions included Brown asymmetric allylation, olefin cross-metathesis, alkyne-epoxide coupling, and macrolactamization. The anti-yeast α-glucosidase activities of penarolide sulfate A2 and its fully desulfated derivative were examined showing IC50 values of 4.87 and 10.74 μg mL−1, respectively.

A new platinum-catalyzed anti-stereocontrolled ring-opening of oxabicyclic alkenes with various Grignard reagents was reported, which afforded the corresponding anti-2-substituted-1,2-dihydronaphthalen-1-ol products with moderate to good yields in the presence of a catalytic amount of Pt(PPh3)4 (2.5 mol%) under mild conditions. The effects of catalyst loading, solvent and temperature on the yield were also investigated. Furthermore, the trans-configuration of the product 5i was confirmed by X-ray diffraction analysis.

New glucuronic acid donors for the modular synthesis of heparan sulfate oligosaccharides by Omkar P. Dhamale; Chengli Zong; Kanar Al-Mafraji; Geert-Jan Boons (2087-2098).
Although hundreds of heparan sulfate (HS) binding proteins have been implicated in a myriad of physiological and pathological processes, very little information is known about ligand requirements for binding and mediating biological activities by these proteins. We report here a streamlined approach for the preparation of modular disaccharide building blocks that will facilitate the assembly of libraries of HS oligosaccharides for structure–activity relationship studies. In particular, we have found that glucuronic acid donors, which usually perform poorly in glycosylations, can give high yields of coupling products when the C-2 hydroxyl is protected with a permanent 4-acetoxy-2,2-dimethyl butanoyl- (PivOAc) or temporary levulinoyl (Lev) ester and the C-4 hydroxyl modified with a selectively removable 2-methylnaphthyl (Nap) ether. It has been shown that the PivOAc ester can be removed without affecting sulfate esters making it an ideal protecting group for HS oligosaccharide assembly. Iduronic acid donors exhibit more favorable glycosyl donating properties and a compound protected with a Lev ester at C-2 and an Fmoc function at the C-4 hydroxyl gave coupling products in high yield. The new donors avoid post-glycosylation oxidation and therefore allow the facile preparation of modular disaccharide building blocks.

An efficient procedure for the syntheses of pyrazolo[1,5-a]pyrimidines through reactions of 1,2-allenic ketones with aminopyrazoles under extremely mild conditions without using any catalyst or promoter has been developed. The reactions showed excellent regio-selectivity with all the allenic ketone substrates except for those bearing an alkyl group at the internal position of the allene moiety. The reason behind this regio-selectivity dissimilarity has been explored with the aid of the B3LYP/6-31G* level of density functional theory. Moreover, this novel procedure has been successfully applied in the preparation of nucleoside-pyrazolo[1,5-a]pyrimidine chimeras with potent antiviral activities.

Concise and scalable asymmetric synthesis of 5-(1-amino-2,2,2-trifluoroethyl)thiazolo[3,2-b][1,2,4]triazoles by Haibo Mei; Yiwen Xiong; Chen Xie; Vadim A. Soloshonok; Jianlin Han; Yi Pan (2108-2113).
This study describes asymmetric Mannich-type additions between C-5 lithiated thiazolo[3,2-b][1,2,4]triazoles and enantiomerically pure (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine. Under the optimized conditions, these reactions proceed with good (up to 78%) chemical yields and virtually complete (98 : 2 to >99 : 1 dr) diastereoselectivity. The same stereochemical outcome was obtained using 1.05 g scale of the starting (3,3,3)-trifluoroacetaldimine. The method developed in this work provides concise and generalized access to thiazolo[3,2-b][1,2,4]triazoles containing a chiral (trifluoro)ethylamine group.

Discovery of potential anti-inflammatory drugs: diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase by Bo Jiang; Xiaojing Huang; Hequan Yao; Jieyun Jiang; Xiaoming Wu; Siyi Jiang; Qiujuan Wang; Tao Lu; Jinyi Xu (2114-2127).
A series of hybrids from diaryl-1,2,4-triazole and hydroxamic acid or N-hydroxyurea were synthesized and evaluated as novel anti-inflammatory agents. The biological data showed that (i) all the compounds showed dual COX-2/5-LOX inhibitory activities in vitro, and 15e showed optimal inhibitory activities (COX-2: IC50 = 0.15 μM, 5-LOX: IC50 = 0.85 μM), (ii) 15e selectively inhibited COX-2 relative to COX-1 with selectivity index (SI = 0.012) comparable to celecoxib (SI = 0.015), (iii) 15e exhibited potent anti-inflammatory activity (inhibition: 54.1%) which was comparable to the reference drug celecoxib (inhibition: 46.7%) in a xylene-induced ear edema assay, and (iv) 15e displayed promising analgesic activity in acetic acid-induced writhing response and hot-plate assay. Finally, a molecular modeling study revealed the binding interactions of 15e with COX-2 and 5-LOX. Our findings suggest that 15e may be a promising anti-inflammatory agent for further evaluation.

Reactions of enantiopure cyclic diols with sulfuryl chloride by Derek R. Boyd; Narain D. Sharma; Magdalena Kaik; Peter B. A. M<sup>c</sup>Intyre; John F. Malone; Paul J. Stevenson (2128-2136).
Monocyclic allylic cis-1,2-diols reacted with sulfuryl chloride at 0 °C in a regio- and stereo-selective manner to give 2-chloro-1-sulfochloridates, which were hydrolysed to yield the corresponding trans-1,2-chlorohydrins. At −78 °C, with very slow addition of sulfuryl chloride, cyclic sulfates were formed in good yields, proved to be very reactive with nucleophiles and rapidly decomposed on attempted storage. Reaction of a cyclic sulfate with sodium azide yielded a trans-azidohydrin without evidence of allylic rearrangement occurring. An enantiopure bicyclic cis-1,2-diol reacted with sulfuryl chloride to give, exclusively, a trans-1,2-dichloride enantiomer with retention of configuration at the benzylic centre and inversion at the non-benzylic centre; a mechanism is presented to rationalise the observation.

Biomimetic aerobic oxidative hydroxylation of arylboronic acids to phenols catalysed by a flavin derivative by Hana Kotoučová; Iveta Strnadová; Martina Kovandová; Josef Chudoba; Hana Dvořáková; Radek Cibulka (2137-2142).
Flavin-catalysed oxidative hydroxylation of substituted arylboronic acids by molecular oxygen with the assistance of hydrazine or ascorbic acid resulted in phenols in high yields. This mild organocatalytic protocol is compatible with a variety of functional groups and it is alternatively usable for transformation of alkylboronic acids to alcohols. Reaction takes place also in water and fulfils criteria for a green procedure.

A fluorescent off–on NBD-probe for F sensing: theoretical validation and experimental studies by Arundhati Roy; Avdhoot Datar; Dnyaneshwar Kand; Tanmoy Saha; Pinaki Talukdar (2143-2149).
The design, synthesis and fluoride sensing ability of a 7-nitro-2,1,3-benzoxadiazole (NBD) based chemodosimeter is reported. Theoretical calculations were used to design a more applicable off–on response, by choosing NBD as the accurate fluorophore. Reaction of the NBD-probe with 300 equivalents of tetrabutyl ammonium fluoride (TBAF) exhibited a response time of 80 minutes and the reaction was selective to F and sensing of the ion was marked by a 110-fold enhancement of green fluorescence. The off–on fluorescence characteristics of the probe enabled its application in live-cell imaging of intracellular F ions.

Back cover (2151-2152).