Recent methods for the synthesis of (E)-alkene units in macrocyclic natural products

(E)-Alkene units are frequently found in macrocyclic natural products. Among the reactions that form the double bond during the cyclization, the classical Horner-Emmons coupling is still frequently used with success. During the last decade, ring-closing metathesis has emerged as a very powerful tool for the synthesis of large rings, but the E/Z selectivity, which is rarely predictable, depends on many factors which will be discussed in this review. The best solution might be a two-step procedure involving ring-closing alkyne metathesis (RCAM) followed by stereoselective reduction of the macrocyclic alkyne unit to the corresponding E double bond.     

Stereo- and regioselective glycosylations to the bis-C-arylglycoside of kidamycin

In explorations toward the total synthesis of the antitumor anthrapyran natural product kidamycin, the regioselective introduction of aminosugars angolosamine and vancosamine as C-arylglycosides has been accomplished onto hydroxylated anthrapyran aglycones. Specifically, the 9,11-dihydroxylated anthrapyran A undergoes sequential glycosylations with angolosamine synthon B and vancosamine synthon C to regio- and stereoselectively afford bis-C-glycoside D corresponding to the C-glycoside pattern of kidamycin.     

Applications of sharpless asymmetric dihydroxylation in the total synthesis of natural products

Sharpless asymmetric dihydroxylation involves the reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form an optically active vicinal diol. This reaction was primarily developed by Sharpless based on the already known racemic Upjohn dihydroxylation. The chiral diols obtained by Sharpless asymmetric dihydroxylation are important intermediates in organic synthesis. Herein, we emphasise the applications of Sharpless asymmetric dihydroxylation in the total synthesis of natural products.     

Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds

The enantiomerically pure chiral benzocyclic amines 6–8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a–c. The method involves: (a) formation of chiral imines 10a–c from the prochiral ketones 9a–c and the inexpensive chiral auxiliary (R)- or (S)-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a–c and 12a–c; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds.     

De novo synthesis of natural products via the asymmetric hydration of polyenes

For the last ten years our group has been working toward the development of an asymmetric hydration approach to polyketide natural products based on the regioselective hydration of di- and tri-enoates. Key to the success of this approach is the recognition that both high regiocontrol and asymmetric induction could be obtained by the use of a Sharpless asymmetric dihydroxylation reaction. Herein we describe the development of the method and its application to natural product total synthesis.     

Organic synthesis using haloboration reaction VIII. Stereo- and regioselective synthesis of [z]-1,2-dihalo-1-alkenes

[Z]-1,2-Dihalo-1-alkenes can be prepared stereo- and regioselectively in good yields from 1-alkynes by the bromoboration with tribromoborane, followed by the treatment with iodine chloride or bromine chloride in the presence of sodium acetate.     

Quinine-catalyzed asymmetric domino Michael-cyclization reaction for the synthesis of spirocyclic oxindoles bearing two spiro quaternary centers and three consecutive stereocenters

An efficient organocatalytic diastereo- and enantioselective method for the construction of spirocyclic oxindole derivatives bearing two spiro quaternary centers and three consecutive stereocenters via a domino Michael/cyclization process has been developed. Using commercially available quinine as catalyst, the reactions of 3-isothiocyanato oxindoles with unsaturated pyrazolones and unsaturated isoxazolones proceeded smoothly under mild reaction conditions for giving two classes of spirocyclic oxindole compounds in high to excellent yields with moderate to good diastereoselectivities and enantioselectivities. A plausible dual activation working model was tentatively proposed to account for the stereochemistry of the domino Michael/cyclization process.     

A concise synthesis of maleic anhydride and maleimide natural products found in Antrodia camphorata

Recently, the natural products maleic anhydride 1 and maleimides 2 and 3 have been isolated from the mycelium of Antrodia Camphorata, each displaying activity in LLC cell lines. We describe a concise synthesis of each of these natural compounds utilizing C-C cross-coupling methodology, namely, the Negishi and Suzuki reactions. This efficient and high yielding synthesis is convergent lending itself to production of medicinal analogues.     

Development of new methods in organic synthesis and their applications to the synthesis of biologically interesting natural products

2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.     

Reactions of sodium selenide with ethynyl and bromoethynyl ketones: Stereo- and regioselective synthesis of functionalized divinyl selenides and 1,3-diselenetanes

A method for the preparation of 2,4-dimethylene-1,3-diselenetanes based on the novel reaction of sodium selenide with bromoethynyl ketones has been developed. New functionalized divinyl selenides have been obtained by regio- and stereoselective addition of sodium selenide to ethynyl ketones.     

Allenes in catalytic asymmetric synthesis and natural product syntheses

Allenes are the simplest class of cumulenes, with two contiguous C=C bonds, and show unique physical and chemical properties. These features make allenes particularly attractive in modern organic chemistry. In this Review, attention is paid to the advances made in catalytic asymmetric synthesis and natural product syntheses based on well-established reactions of allenes, such as propargylation, addition, cycloaddition, cycloisomerization, cyclization, etc., with or without catalysts. Their versatile reactivity, substituent-loading ability, axial to center chirality transfer, and controllable selectivity allow access to target molecules by unique and efficient approaches. The main topics in this Review are presented with selected examples from 2003 to 2011.     

Comparison of three methods for natural gas dehydration

This paper compares three methods for natural gas dehydration that are widely applied in industry:(1) absorption by triethylene glycol, (2) adsorption on solid desiccants and (3) condensation. A comparison is made according to their energy demand and suitability for use. The energy calculations are performed on a model where 105 Nm3/h water saturated natural gas is processed at 30 °C. The pressure of the gas varies from 7 to 20 MPa. The required outlet concentration of water in natural gas is equivalent to the dew point temperature of -10 °C at gas pressure of 4 MPa.     

The manganese-mediated regioselective chlorination of allenes in synthetic approaches towards the spongistatins and halomon natural products

The first examples for the chlorination of allenes using manganese reagents generated from potassium permanganate and benzyl triethylammonium chloride in the presence of the chlorine donors oxalyl chloride or chlorotrimethylsilane are reported with the aim of developing useful synthetic routes to the spongistatin and halomon marine natural products.     

Dearomatization strategies in the synthesis of complex natural products

Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemoselective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures.