Yuan-Ping Ruan

Highly Enantioselective Henry Reactions of Aromatic Aldehydes Catalyzed by an Amino Alcohol-Copper(II) Complex

Amino alcohol-Cu(II) catalyst: Highly enantioselective Henry reactions between aromatic aldehydes and nitromethane have been developed. The reactions were catalyzed by an easily available and operationally simple amino alcohol-copper(II) catalyst. In total, 38 substrates were tested and the R-configured products were obtained in good yields with excellent enantioselectivities.

SmI2-Mediated Radical Cross-Couplings of α-Hydroxylated Aza-hemiacetals and N,S-Acetals with α,β-Unsaturated Compounds: Asymmetric Synthesis of (+)-Hyacinthacine A2, (−)-Uniflorine A, and (+)-7-epi-Casuarine

The SmI(2)-mediated radical coupling reactions of β-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with α,β-unsaturated compounds are described. This method allows a rapid access to β-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids hyacinthacine A(2) (2), uniflorine A (3, 6-epi-casuarine), and the unnatural epimer 7-epi-casuarine (37) have been synthesized in four and five steps with overall yields of 34%, 16%, and 13%, respectively. The radical mechanism of the coupling reactions has been confirmed by controlled experiments, which also allowed deducing the anionic mechanism in the coupling between N,S-acetal 6 and carbonyl compounds. This demonstrates that the mechanisms of these SmI(2)-mediated reactions are switchable from Barbier-type anionic to radical by cooperative action of BF(3)·OEt(2) and t-BuOH.

A Flexible Approach to Azasugars: Asymmetric Total Syntheses of (+)-Castanospermine, (+)-7-Deoxy-6-epi-castanospermine, and (+)-1-epi-Castanospermine

The asymmetric total synthesis of natural azasugars (+)-castanospermine, (+)-7-deoxy-6-epi-castanospermine, and synthetic (+)-1-epi-castanospermine has been accomplished in nine to ten steps from a common chiral building block (S)-8. The method features a powerful chiral relay strategy consisting of a highly diastereoselective vinylogous Mukaiyama-type reaction with either chiral or achiral aldehydes (> or = 95% de; de=diastereomeric excess) and a diastereodivergent reduction of tetramic acids, which allows formation of three continuous stereogenic centers with high diastereoselectivities. The method also provides a flexible access to structural arrays of 5-(alpha-hydroxyalkyl)tetramic acids, such as 17/34, and 5-(alpha-hydroxyalkyl)-4-hydroxyl-2-pyrrolidinones, such as 18 and 25/35 a. The method constitutes the first realization of the challenging chiral synthons A and D and thus of the conceptually attractive retrosynthetic analysis shown in Scheme 1 in a highly enantioselective manner.

syn‐ and Enantioselective Henry Reactions of Aliphatic Aldehydes and Application to the Synthesis of Safingol

Fundamental Research Funds for the Central Universities [2010121014]; Natural Science Foundation of Fujian Province [2013J10011]

Asymmetric Total Synthesis of (-)-Awajanomycin

The first asymmetric total synthesis of the unnatural enantiomer of cytotoxic awajanomycin (1) is reported. The synthetic approach features first a convergent strategy using the cross-olefin metathesis reaction to link the lipid side chain 2 and the piperidinone core structure 3. The second feature of the synthesis resides on the construction of segment 3 from the building block 5 via a three-component tandem reaction on the mixed imide 12. Through this work, the stereochemistry at C-11 and the absolute configuration of awajanomycin were established as 3R,5R,6S,8S,11S.

Diastereoselective synthesis and bioactivity of long-chain anti-2-amino-3-alkanols

An improved four-step approach for the stereoselective synthesis of long-chain anti-2-amino-3-alkanols is described. Using this method, the syntheses of antiproliferative (antitumoral) compounds, spisulosine (ES-285, 2), clavaminols A and B (3 and 4), the deacetylated products of clavaminols H and N (7 and 8), as well as (2S,3R)-2-aminododecan-3-ol (9) and xestoaminol C (10), have been achieved in excellent diastereoselectivities. In vitro study showed that these compounds induced cell death and dose-dependently inhibited cell proliferation in human glioblastoma cell line SHG-44, indicating the anti-tumor property of this series of compounds.

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the (13) C NMR spectrum, the (13) C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.

Organocatalytic, Asymmetric Total Synthesis of (−)-Haliclonin A

The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.

A Practical Two‐Step Synthesis of 3‐Alkyl‐2,3‐dihydro‐1H‐isoindolin‐1‐ones

Abstract A flexible approach to 3‐alkyl‐2,3‐dihydro‐1H‐isoindolin‐1‐ones via the reductive‐alkylation procedure is described. Present method is versatile in scope, allowing the easy introduction of various C‐3 carbon‐substituents by Grignard addition to phthalimide.

Stereodivergent and enantioselective total syntheses of isochaetominines A–C and four pairs of isochaetominine C enantiomers: a six-step approach

The first enantioselective and stereodivergent total syntheses of (−)-isochaetominines A–C and all eight 2,3-cis-stereoisomers of (−)-isochaetominine C, including the natural (+)-14-epi-isochaetominine C, and the proposed structures of (−)-pseudofischerine (2) and (−)-aniquinazoline D (3), have been achieved. The stereodivergent approach relies on the DMDO-initiated divergent tandem reaction to give a separable mixture of two products, a monocyclization product and a diastereomer of isochaetominine C (or a homologue) as a result of double cyclization. An epimerization-free two-step protocol has been developed for the highly diastereoselective transformation of the former product into an isochaetominine-type compound with characteristic 3,14-cis-stereochemistry. As a result of our synthetic efforts, the structures of the natural (−)-pseudofischerine and (−)-aniquinazoline D have been revised both as (−)-isochaetominine C (6).