A formal total synthesis of Lycopodium alkaloid, (±)-magellanine, by using the intramolecular Pauson Khand reaction

A formal total synthesis of magellanine was accomplished by using the stereoselective Ireland-Claisen rearrangement and the intramolecular Pauson-Khand reaction of exocyclic enynes as key steps.     

Total synthesis of (±)-brazilin and formal synthesis of (±)-brazilein, (±)-brazilide A using m-CPBA

Total synthesis of (±)-brazilin has been accomplished. m-CPBA epoxidation of allyl alcohol 10 and epoxy opening reaction mediated by m-chlorobenzoic acid, formed in situ as a byproduct, gave advanced intermediate diol 14. O-alkylation and cyclization gave phenol 6 which enabled the formal synthesis of (±)-brazilein and (±)-brazilide A.     

A new approach to the bicyclo[4.3.0] ring system of natural products from the liverwort: total synthesis of (±)-chiloscyphone and (±)-isochiloscyphone

Construction of the tricyclic derivative 5, a common intermediate for the synthesis of sesquiterpenoids 1-4, was accomplished by using the intramolecular Diels-Alder reaction. Availability of 5 was demonstrated by effective total synthesis of chiloscyphone 1 and isochiloscyphone 2.     

A formal synthesis of (±) lycoramine via an intramolecular Heck reaction

The first use of an intramolecular Heck reaction for the construction of the quaternary centre of a galanthamine-like Amaryllidaceae alkaloid is described. The use of the acetate anion is shown as an activating factor in the 6-exo cyclisation of 5.     

Use of a highly effective intramolecular Pauson-Khand cyclisation for the formal total synthesis of (±)-α- and β-cedrene by preparation of cedrone

The cedrene carbon skeleton was directly and efficiently assembled from a simple monocyclic precursor by the strategic use of a high yielding intramolecular Pauson-Khand cyclisation reaction. A small number of further synthetic manipulations provided a concise formal total synthesis of α- and β-cedrene. The cyclisation precursor was readily prepared, with a stereoselective ketone alkenylation selectively providing the olefin required for efficient access to the natural target.     

Total synthesis of (±)-debromoflustramine B and E and (±)-debromoflustramide B based on one-pot intramolecular Ullmann coupling and Claisen rearrangement

Total syntheses of (±)-debromoflustramine B and E and (±)-debromoflustramide B were accomplished using a common and versatile intermediate spirocyclic oxindole 14, which was concisely prepared through intramolecular Ullmann coupling and Claisen rearrangement from iodoindole 13 on a multigram scale.     

Synthesis of (±)-coerulescine and a formal synthesis of (±)-horsfiline

A straightforward synthesis of (±)-coerulescine and (±)-horsfiline has been established from 3-formyl-3-phenylpyrrolidine employing 4-hydroxypiperidine as the starting material. There are two remarkable steps for the synthesis of (±)-coerulescine and (±)-horsfiline. One is the rapid access to produce 3-formyl-3-phenylpyrrolidine by Lewis acid-catalyzed rearrangement of 3,4-dihydroxy-4-phenylpiperidine. The other key step is an intramolecular electrophilic cyclization from 3-benzylcarbamoyl-3-phenylpyrrolidine to the 3,3-spirocyclic 2-oxindole ring skeleton.     

Stereoselective total synthesis of (±)-α-vetispirene, (±)-hinesol, and (±)-β-vetivone based on a Claisen rearrangement

The stereoselective total syntheses of (±)-α-vetispirene, (±)-hinesol, and (±)-β-vetivone were accomplished based on a Claisen rearrangement in an alkenyl bicyclic dihydropyran system. The most striking feature of this approach is that the Claisen rearrangement of bicyclic dihydropyran proceeds stereoselectively to provide a multi-functionalized spiro[4.5]decane, which is an efficient precursor for the synthesis of the vetivane sesquiterpenes.     

Protecting group free syntheses of (±)-columbianetin and (±)-angelmarin

A five-step and protecting group free synthesis of (±)-columbianetin from cyclohexane-1,3-dione is reported. The former compound was converted into its p-hydroxycinnamate derivative, (±)-angelmarin, using Coster’s esterification procedure. Efforts to modify the synthesis so as to prepare angelmarin and columbianetin in an enantioselective manner are described.     

Synthesis of the necine bases (±)-macronecine and (±)-supinidine via an aza-ene reaction and allylsilane induced ring closure

An aza-ene reaction has been used for the first time for the synthesis of two 5-membered lactam-hydrazides, each with a built-in allylsilane terminator for further elaboration. One of the lactam-hydrazides was transformed via an allylsilane-hydrazonium ion ring closure to a fused tetrahydropyrazole which may be considered as a mono-nitrogen analog of the biologically significant necine bases. A density functional theoretical study (B3LYP/6-21G*) was undertaken to provide insight into the factors that favor a synclinal transition structure of the hydrazonium ion intermediate leading to the tetrahydropyrazole. This stereocontrolled synthesis served as a model for the multi-step conversion of the other lactam-hydrazide, the substituted 2-pyrrolidinone, to necine bases (±)-supinidine and (±)-macronecine. An allylsilane-aldehyde ring closure formed the key step in the synthesis of these natural products.     

First total syntheses of (±)-3-aza-11-selena and (±)-3-aza-11-tellura steroids

An efficient synthesis of 11-selena and 11-tellura steroids bearing a pyridine as an A ring was achieved via an intramolecular Diels-Alder cycloaddition of o-quinodimethanes, which were generated from a 3-azabicyclo[4.2.0]octa-1,3,5-trien-7-one ketal. The major isomer matches the trans-anti-trans ring configuration of natural products. Finally, the vinyl groups of the synthesized 11-hetero steroids have been oxidized by the Wacker process in good yields. The characteristic ¹H and ¹³C NMR spectroscopic features of the synthesized compounds are reported.     

An efficient synthesis of 2-(guaiazulen-1-yl)furan derivatives via intramolecular Wittig reactions

An efficient and mild synthesis of 2-(guaiazulen-1-yl)furans,starting from easily accessible 1-(3-aryl-2-cyanopropenoyl) guaiazulenes,tributylphosphine and acyl chlorides,is described.The strategy employs the intramolecular Wittig protocol as a key step to append the crticial furan ring,leading to the highly functional furans in good yields.     

A stereoselective total synthesis of (±)-tormesol

A general strategy for the synthesis of both trans/syn- and trans/anti-sphenolobane diterpenes has been developed, which utilizes an intramolecular ester enolate alkylation (IEEA) as a key step. A stereoselective total synthesis of (±)-tormesol (1), an unusual trans/syn-sphenolobane diterpene, was accomplished in 18 steps in 4.1% overall yield from readily available aldehyde 16.     

Total synthesis of (±)-β-chamigrene and (±)-laurencenone C via Ireland ester Claisen rearrangement and an intramolecular type II carbonyl ene reaction sequence

A combination of Ireland ester Claisen rearrangement and intramolecular type II carbonyl ene reactions were exploited for the total synthesis of chamigrenes containing a quaternary carbon atom next to the spirocentre in spiro[5.5]undecane.     

Efficient syntheses of (±)-hydrangenol, (±)-phyllodulcin and (±)-macrophyllol

In this paper we report on a efficient and flexible synthetic route towards the total syntheses of the dihydrocoumarine derivatives hydrangenol (1), phyllodulcin (1a) and macrophyllol (6b). The syntheses started with a readily available phosphonium salt 2 and suitable modified benzaldehydes 3/3a/3b resulting in 46 to 61% overall yields in three to four-steps sequences. The racemic products could be separated by chiral HPLC. The evidence of the (R)-enantiomer for sweetness could be demonstrated for 1a.     

Montmorillonite K10 clay-catalyzed synthesis of homoallylic silyl ethers: an efficient and environmentally friendly Hosomi-Sakurai reaction

Aromatic aldehydes react with allyltrimethylsilane in the presence of activated Montmorillonite K10 clay to give homoallylic silyl ethers in good to excellent yields.     

A formal total synthesis of (±)-9-isocyanoneopupukeanane

A formal total synthesis of the marine sesquiterpene (±)-9-isocyanoneopupukeanane starting from the readily available monoterpene carvone has been accomplished employing a combination of intermolecular Michael addition-intramolecular Michael addition reaction and an intramolecular rhodium carbenoid C-H insertion reaction as key steps, and identifying the isopropenyl group as a masked hydroxy group.     

First total synthesis of (±)-puyanin and (±)- 4′-O-methylbonannione

A facile approach for the first total synthesis of two naturally occurring geranylated flavonoids, (±)-puyanin 1 and (±)-4′-O-methylbonannione 2 have been obtained with total yield 27% and 21%, respectively. The key steps were regioselective cyclization of geranylated tetrahydroxychalcone and regioselective geranylation of 2, 4, 6-trihydroxy- acetophenone.     

Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction

A catalytic process for the synthesis of optically active C4-substituted tetrahydroindandiones using an asymmetric intramolecular aldol condensation reaction was developed. When 30 mol% of phenylalanine and 50 mol% of pyridinium p-toluenesulfonate were used under highly concentrated conditions, a variety of C4-substituted tetrahydroindandiones and octahydronaphthalenediones were obtained in high yield (up to 89% yield) and high enantiomeric excess (up to 94% ee). One of the products was successfully transformed into the key intermediate for the synthesis of the phosphatidylinositol 3-kinase inhibitor wortmannin, achieving formal total synthesis of (+)-wortmannin.     

Synthesis of (±)-kuwanon V and (±)-dorsterone methyl ethers via Diels-Alder reaction

The mulberry Diels-Alder adducts, the pentamethyl ethers of kuwanon V 1a and dorsterone 2a were synthesised via a biomimetic intermolecular [4+2] cycloaddition reaction between a highly electron-rich dienophile and a Lewis acid sensitive diene derived from chalcone. Cycloaddition under thermal conditions afforded 1a and 2a (in 3:2 ratio). Cycloaddition catalysed by AgOTf/Bu₄NBH₄ gave higher yields of the adducts.