Helvetica Chimica Acta

doi: 10.1002/hlca.200890237pmid: N/A

Seebach, Dieter; Grošelj, Uroš; Badine, D. Michael; Schweizer, W. Bernd; Beck, Albert K.

doi: 10.1002/hlca.200890216pmid: N/A

Reaction of 2‐phenylacetaldehyde with the Me3Si ether of diphenyl‐prolinol, with removal of H2O, gives a crystalline enamine (1). The HBF4 salts of the MePh2Si ether of diphenyl‐prolinol and of 2‐(tert‐butyl)‐3‐methyl‐ and 5‐benzyl‐2,2,3‐trimethyl‐1,3‐imidazolidin‐4‐one react with cinnamaldehyde to give crystalline iminium salts 2, 3, and 4. Single crystals of the enamine and of two iminium salts, 2 and 3, were subjected to X‐ray structure analysis (Figs. 1, 2, and 6), and a 2D‐NMR spectrum of the third iminium salt was recorded (Fig. 7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five‐membered heterocycles, i.e., D, E (Scheme 2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl‐prolinol derivatives (from the Cambridge File CSD; Table 1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig. 4). The iminium ions 3 and 4 are compared with N‐acylated imidazolidinones F and G (Figs. 9, 12, and 13, and Table 3), and common structural aspects such as minimalization of 1,5‐repulsion (the ‘A1,3‐effect’), are discussed. The crystal structures of the simple diphenyl‐prolinol⋅HBF4 salt (Fig. 3) and of Boc‐ and benzoyl‐(tert‐butyl)methyl‐imidazolidinone (Boc‐BMI and Bz‐BMI, resp.; Figs. 10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high‐level‐of‐theory DFT calculations (Figs. 5 and 8, and Table 2). Delicate details including pyramidalization of trigonal N‐atoms, distortions around iminium CN bonds, shielding of diastereotopic faces, and the π‐interaction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations.

Capone, Stefania; Kieltsch, Iris; Flögel, Oliver; Lelais, Gerald; Togni, Antonio; Seebach, Dieter

doi: 10.1002/hlca.200890217pmid: N/A

The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF3 groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7–14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by 1H‐, 13C‐, and 19F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed.

Zhang, Li‐Peng; Bao, Yong; Kuang, Yun‐Yan; Chen, Fen‐Er

doi: 10.1002/hlca.200890218pmid: N/A

A six‐step asymmetric total synthesis of (20S)‐camptothecin (1) has been accomplished in 25% overall yield starting from the known pyridone 3. The key steps in this synthesis are the chemoselective Ni‐catalyzed hydrogenation of 3‐cyanopyridone 6 to 3‐formylpyridone 7 in AcOH/pyridine/H2O and the Davis asymmetric hydroxylation of tricyclic lactone 4 utilizing a chiral N‐sulfonyloxaziridine into (4′S)‐tricyclic hydroxylactone 2.

Chen, Wei‐Min; Cheng, Chao; Li, Bing‐Zhou; Ho, Tse‐Lok; Cai, Zhao‐Shuo; Wang, Yuqiang; Sun, Ping‐Hua

doi: 10.1002/hlca.200890219pmid: N/A

The use of pyridine‐4‐thiol (PT) to preserve certain aryl bromides in strong alkali is reported (Scheme 1). The presence of this additive or of some of its amphoteric analogs such as 3‐hydroxypyridin‐4(1H)‐ones suppresses the replacement of the Br‐substituent by hydroxide and alkoxide ions. A mechanistic interpretation of the effect is proposed.

Jia, Rui; Guo, Yue‐Wei; Mollo, Ernesto; Gavagnin, Margherita; Cimino, Guido

doi: 10.1002/hlca.200890220pmid: N/A

Two new bis‐cembranoids, ximaolides F (1) and G (2), were isolated from the Hainan soft coral Sarcophyton tortuosum. The structures and relative configurations of the two new compounds were elucidated by the combination of spectroscopic methods, chemical conversion of ximaolide F (1) into ximaolide G (2), and comparison with related model compounds.

Xin, Hai‐Liang; Xu, Yan‐Feng; Hou, Yin‐Huan; Zhang, Ya‐Ni; Yue, Xiao‐Qiang; Lu, Jin‐Cai; Ling, Chang‐Quan

doi: 10.1002/hlca.200890221pmid: N/A

Two novel triterpenoids, (2α,3α)‐3‐{[4‐O‐(β‐D‐glucopyranosyl)‐β‐D‐xylopyranosyl]oxy}‐2,23‐dihydroxy‐30‐methoxy‐30‐oxoolean‐12‐en‐28‐oic acid (1) and (2α,3α)‐2,23,30‐trihydroxy‐3‐[(β‐D‐xylopyranosyl)oxy]olean‐12‐en‐28‐oic acid (2) were isolated from Portulaca oleracea L., and they both showed weak cytotoxic activity assayed with the MTT method.

Venkateswarlu, Katta; Satyalakshmi, Gandham; Suneel, Kanaparthy; Reddy, Thummala Sreenivasulu; Raju, Tuniki Venugopal; Das, Biswanath

doi: 10.1002/hlca.200890222pmid: N/A

Methyl 5‐formyl‐1‐benzofuran‐6‐carboxylate (1) and the two clerodane diterpenes, methyl 6‐oxocleroda‐3,13‐dien‐15,16‐olid‐18‐oate (2) and 2β‐(2‐methylbutanoyl)cleroda‐3,13‐dien‐15,16‐olid‐18‐oic acid (3), together with 15 known compounds, were isolated from the aerial parts of Pulicaria wightiana. The structures of the new compounds 1, 2, and 3 were established by spectroscopic (mainly 1D‐ and 2D‐NMR) methods.

Beynek, Nesrin; Uluçam, Gühergül; Benkli, Kadriye; Koparal, Ays̨e Tansu

doi: 10.1002/hlca.200890223pmid: N/A

In the present work, we describe the synthesis and characterization of five new versatile acyclic or macrocyclic ligands containing binaphthyl‐linked pyridine, bipyridine, or phenanthroline groups in their framework (see Schemes 1–4). The structures of the ligands were elucidated on the basis of elemental analyses, IR, 1H‐NMR, 13C‐NMR, and FAB mass spectra. The cytotoxicity of these compounds was tested in vitro by using the tetrazolium salt reduction (MTT) assay on A549 (human lung carcinoma epithelial like) cells. All of the tested compounds induced time‐ and concentration‐dependent cytotoxic effect.

Mimaki, Yoshihiro; Watanabe, Kazuki

doi: 10.1002/hlca.200890224pmid: N/A

Phytochemical analyses were carried out on the rhizomes of Clintonia udensis (Liliaceae) with particular attention paid to the steroidal glycoside constituents, resulting in the isolation of three new polyhydroxylated spirostanol glycosides, named clintonioside A (1), B (2), and C (3). On the basis of their spectroscopic data, including 2D‐NMR spectroscopy, in combination with acetylation and hydrolytic cleavage, the structures of 1–3 were determined to be (1β,3β,23S,24S,25R)‐1,23,24‐trihydroxyspirost‐5‐en‐3‐yl O‐β‐D‐glucopyranosyl‐(1→4)‐O‐[α‐L‐rhamnopyranosyl‐(1→2)]‐β‐D‐glucopyranoside (1), (1β,3β,23S,24S)‐3,21,23,24‐tetrahydroxyspirosta‐5,25(27)‐dien‐1‐yl O‐α‐L‐rhamnopyranosyl‐(1→2)‐O‐[β‐D‐xylopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (2), and (1β,3β,23S,24S)‐21‐(acetyloxy)‐24‐[(6‐deoxy‐β‐D‐gulopyranosyl)oxy]‐3,23‐dihydroxyspirosta‐5,25(27)‐dien‐1‐yl O‐α‐L‐rhamnopyranosyl‐(1→2)‐O‐[β‐D‐xylopyranosyl‐(1→3)]‐β‐D‐glucopyranoside (3).