Acyloins from Morita-Baylis-Hillman adducts: an alternative approach to the racemic total synthesis of bupropion

In this Letter, we describe an easy and straightforward strategy for the preparation of acyloins (α-hydroxyketones) from Morita-Baylis-Hillman adducts, based on a Curtius rearrangement. Different acyloins were obtained with good overall yield (>40% for three steps). To exemplify the synthetic usefulness of this strategy, total synthesis of (±)-bupropion, a dopamine, and nor-epinefrine reuptake inhibitor has been accomplished in eight steps with an overall yield of 25%.     

Mechanism and synthesis of pharmacologically active quinolones from Morita-Baylis-Hillman adducts

The synthesis of quinolones from Morita-Baylis-Hillman (MBH) adducts is reported. The quinolone skeleton is formed via a TFA-mediated cyclization of the MBH adduct, and a mechanism study using ESI(+)-MS(/MS) has indicated the role played by TFA in this key reaction step. The total syntheses of Norfloxacin and a benzyl quinolone carboxylic acid (BQCA) derivative are described. Norfloxacin is a fluoroquinolonic antibacterial drug whereas BQCA is M₁ receptor positive allosteric modulator and seem to provide access to new potential drugs for Alzheimer disease, pain, and sleep disorders. The syntheses of these two important quinolones exemplify the versatility and potentiality of the approach.     

Highly diastereoselective total synthesis of the anti-tumoral agent (±)-Spisulosine (ES285) from a Morita-Baylis-Hillman adduct

We disclose herein a new approach for the highly diastereoselective total synthesis of the anti-tumoral agent (±)-Spisulosine. The synthesis was accomplished in seven steps with an overall yield of 10%. The key step involves the transformation of a Morita-Baylis-Hillman into an acyloin, which was subsequently used as substrate in a highly diastereoselective reductive amination reaction.     

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol, starting from commercially available 3,5-dimethoxybenzoic acid, have been achieved by a sequential process. The overall synthetic strategy involves Nazarov cyclization, Ramberg-Backlund olefination, and Friedel-Crafts alkylation.     

Short and efficient synthesis of a stock material of dihydroxyacetone phosphate from glycidol

As enzymatic syntheses are expensive for a large-scale preparation of DHAP, a precursor leading to DHAP was synthesized in three steps starting from (±) glycidol; the stable benzylated stock material afforded by hydrogenolysis DHAP in high purity, which may be used directly without purification in enzymatic aldol synthesis.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Stereoselective synthesis and determination of the cytotoxic properties of spicigerolide and three of its stereoisomers

Stereoselective syntheses of the naturally occurring, cytotoxic lactone spicigerolide and three nonnatural stereoisomers thereof are described. The commercially available sugar l-rhamnose was in all cases the chiral starting material. Key steps in each of these syntheses were asymmetric Brown allylations and ring-closing metatheses. The cytotoxic activities of the four lactones against a range of tumoral lines were then determined.     

A concise synthesis of (±)-3-deoxyisoaltholactone

The novel styryl lactone analog (±)-3-deoxyisoaltholactone was synthesized in 5 steps from dihydrofuran. An intramolecular vinylsilane–oxocarbenium condensation thus afforded the central cis-fused bicyclic ether array in near quantitative yield as a single stereoisomer.     

A short synthesis of some monoterpenoids from the adduct of myrcene with benzenesulfinyl chloride

The title adduct was converted into 1,2-epoxymyrcene; its cationic 5-exo-cyclization gave a (±)-hop ether having the iridane-type skeleton. Effective syntheses of a furanoterpene perillene and some functionalized cyclopentanoid monoterpenes regioisomeric to iridoids were elaborated using sulfur-containing geraniol derivatives easily accessible from the same adduct in a synthetic sequence including the Pummerer reaction and anionic cyclization.Deceased Nov., 1, 1992.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 113–117, January, 1993.     

(±)-Mesembrine的全合成

以3-乙氧基-2-环己烯酮羰基邻位芳基化反应与Tsuji-Trost反应的串联反应作为关键步骤来构筑季碳中心, 完成了番杏科生物碱Mesembrine的全合成. 从商品化原料出发经6步反应以17.8%的总收率合成得到(±)-Mesembrine.     

An approach for the enantioselective synthesis of biologically active furanones from a Morita-Baylis-Hillman adduct

Herein, we disclose an approach for the asymmetric synthesis of both enantiomers of an anti-inflammatory furanone. The approach is based on the utilization of a Morita-Baylis-Hillman adduct as starting material and has as key step a selective epoxide-opening/benzylic oxidation mediated by Palladium (II). This sequence afforded an advanced intermediate, which was used to accomplish the total synthesis. Experimental evidences allowed us to suggest a mechanistic proposal for the oxidation Palladium(II)-mediated.     

Phosphine-catalyzed cascade [3 + 2] cyclization-allylic alkylation, [2 + 2 + 1] annulation, and [3 + 2] cyclization reactions between allylic carbonates and enones

The phosphine-catalyzed annulations between Morita-Baylis-Hillman adduct carbonates and enones are reported. Under the catalysis of PBu(3) (20 mol %), cascade [3 + 2] cyclization-allylic alkylation, [2 + 2 + 1] annulation, and [3 + 2] cyclization reactions chemoselectively occur depending on the substituent variation of both the carbonate and enone. These reactions provide efficient syntheses of highly functionalized cyclopentenes and cyclopentanes.     

Total syntheses of (±)-frondosin C and (±)-8-epi-frondosin C via a tandem anionic 5-exo dig cyclization-Claisen rearrangement sequence

Microwave-assisted anionic 5-exo dig cyclization-Claisen rearrangement sequence has been investigated as a convenient ‘one-pot’ route to fused cycloheptanoid ring systems. This process was used as the key transformation to construct the tetracyclic framework of frondosin C. Subsequent manipulation of the core allowed the first total syntheses of (±)-frondosin C and (±)-8-epi-frondosin C in a combined overall yield of 20.8% over 14 steps.     

大环二萜天然产物(±)-Sinulariol-A的全合成

以香叶醇为起始原料,经多步反应完成了西松烷型大环二萜类天然产物(±)-Sinulariol-A的全合成.合成的关键步骤是醛5与丙烯酸甲酯经改进的Morita-Baylis-Hillman加成以及二价铬诱导的烯丙基氯化物与醛的分子内加成环化     

Total Synthesis of (2Z)‐[(4R,5R,6S)‐6‐(β‐D‐Glucopyranosyloxy)‐4,5‐dihydroxycyclohex‐2‐en‐1‐ylidene]ethanenitrile,a Cyanoglucoside from Ilex warburgii

The total synthesis of the noncyanogenic cyanoglucoside 1 , originally isolated from Ilex warburgii, was achieved in nine steps (9% overall yield), starting from an optically pure Diels–Alder adduct ((+)‐ 3 ). The key step of the synthesis, the glycosidation, was carried out under Koenigs–Knorr conditions closely related to those developed for the total syntheses of (?)‐lithospermoside and (?)‐bauhinin. We had to tune the protecting groups used for the two free cis‐configured OH groups of the aglycone, which afforded the desired β‐d‐ glucoside intermediate 15 in very good yield (62%).     

The first total synthesis of (±)-lagopodin A

The first total synthesis of (±)-lagopodin A and a formal total synthesis of enokipodins A and B is described. The requisite precursors containing two vicinal quaternary carbon atoms were assembled employing Claisen rearrangement and an RCM reaction as key steps starting from 2,5-dimethoxy-4-methylacetophenone.     

Kinetics and mechanism of the reaction of 1-benzoyloxy-4-[4-(dimethylamino)styryl]pyridinium tetrafluoborate with trimethyl-benzylammonium chloride in acetonitrile

The reaction of 1-benzoyloxy-4-[4-(dimethylamino)styryl]pyridinium tetrafluoborate with trimethylbenzylammonium chloride in acetonitrile takes place with the formation of an ion pair of 1-benzoyloxy-4-[4-(dimethylamino)styryl]pyridinium chloride, the slow decomposition of which to the σ adduct is rate-determining. The equilibrium constants of the individual steps of formation of ions from the ionogens PhCOCl and DASPO are determined. L. M. Litvinenko Institute of Physical Organic Chemistry and Carbon Chemistry, National Academy of Sciences of Ukraine, 70 Lyuksemburg ul., Donetsk 341114, Ukraine. Translated from Teoreticheskaya i éksperimental’naya Khimiya, Vol. 34, No. 3, pp. 148–152, May–June, 1998.     

Stereoselective synthesis of 3-spiro-α-methylene-γ-butyrolactone oxindoles from Morita-Baylis-Hillman adducts of isatin

A concise stereoselective synthesis of 3-spiro-α-methylene-γ-butyrolactone oxindoles from Morita-Baylis-Hillman adducts of isatin in excellent yield has been achieved following a three-step reaction sequences viz. (1) Isomerisation of the Morita-Baylis-Hillman adducts of isatin with trimethyl orthoformate and montmorillonite K10 clay catalyst, (2) a second Morita-Baylis-Hillman reaction with formaldehyde, and (3) an acid catalysed lactonization. The structure and stereochemistry of the products were assigned by X-ray crystallographic and NMR spectroscopic studies. Formation and mechanism of the minor product spirofuran oxindoles and a one-pot base promoted second Morita-Baylis-Hillman adduct formation-lactonization reaction have also been achieved.     

A bidirectional approach to the synthesis of a complete library of adjacent-bis-THF annonaceous acetogenins

Thirty-six stereoisomers of bifunctional adjacent bis-THF (tetrahydrofuran) lactones have been synthesized, which can afford a complete library of the adjacent bis-THF Annonaceous acetogenins. The bis-THF lactones were synthesized, starting from the enantioselectively pure 8,9:12,13-(E,E and Z,E)-16-benzyloxy-5-hydroxy-hexadeca-1,4-olide, in a highly distereoselective manner using oxidative reactions, including rhenium(VII) oxides-mediated oxidative cyclization, Shi's asymmetric epoxidation, and Sharpless asymmetric dihydroxylation reactions. Using the nonsymmetrical bis-THF lactones, syntheses of two nonnatural acetogenins were achieved.     

A three-step total synthesis of goniothalesdiol A using a one-pot Sharpless epoxidation/regioselective epoxide ring-opening

Using a one-pot Sharpless asymmetric epoxidation/regioselective epoxide ring-opening as a key step, the protecting-group-free total synthesis of goniothalesdiol A was accomplished in only three steps starting from commercially available trans-cinnamaldehyde in 55.1% overall yield. In 6 previously reported total syntheses, 6–11 steps were required.