Formal syntheses of (+/-)-pinnaic acid and (+/-)-halichlorine

[chemical reaction: see text]. Concise formal syntheses of marine alkaloids (+/-)-pinnaic acid (1) and (+/-)-halichlorine (2) have been accomplished from a common intermediate. The syntheses illustrate the utility of selective olefin cross metathesis methodologies for the elaboration of advanced synthetic intermediates in complex molecule synthesis.     

Total synthesis of (+/-)-didehydrostemofoline (asparagamine A) and (+/-)-isodidehydrostemofoline

The first total syntheses of (+/-)-didehydrostemofoline (1) and (+/-)-isodidehydrostemofoline (3) are reported. The synthesis begins with the Diels-Alder reaction of readily available pyrrole 9 and ethyl (E)-3-nitroacrylate, the latter serving as a regioinverted equivalent of ketene. After hydrogenation to prevent retro-Diels-Alder reaction, the major cycloadduct is transformed to 7-azabicyclo[2.2.1]heptanol 14. Aza-Cope-Mannich reaction of the formaldiminium derivative of 14 delivers 1-azatricyclo[5.3.0.04.10]decane 15, which in 15 additional steps is converted to 1 and 3.     

Stereocontrolled synthesis of polyfunctionalized cis-decalins from 2-methoxyphenols: total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane

A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is described, involving oxidation of 2-methoxyphenol, intermolecular Diels-Alder reaction, olefination, and Cope rearrangement. Application of this efficient strategy to the total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane was accomplished from creosol and ethyl vinyl ketone via a common intermediate 21.     

Acid-catalyzed cyclization of 2,3-dibenzylidenesuccinates: synthesis of lignans (+/-)-cagayanin and (+/-)-galbulin.

Acid-catalyzed cyclizations of E,E-dibenzylidenesuccinate esters have been developed as an efficient synthetic route to 1-aryl-1,2-dihydronaphthalenes. This reaction has been used in the synthesis of the naturally occurring lignans (+/-)-cagayanin and (+/-)-galbulin.     

First total synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone

[reaction: see text] A simple synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone has been achieved through a common hexahydrofluorenone intermediate obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane.     

Biomimetic synthesis of (+/-)-9,10-deoxytridachione

A tandem Suzuki-coupling/electrocyclisation reaction sequence was employed for the biomimetic synthesis of (+/-)-9,10-deoxytridachione.     

Formal synthesis of (+/-)-platensimycin

A formal total synthesis of (+/-)-platensimycin [(+/-)-1] is reported involving an intramolecular Stetter reaction and a radical cyclization.     

Total Synthesis of (+/-)-Leporin A

An efficient synthesis of (+/-)-leporin A (1) has been developed using a tandem Knoevenagel condensation-inverse electron demand intramolecular hetero Diels-Alder reaction to construct the key tricyclic intermediate 3 from pyridone 5 and dienal 6 in one pot in 35% yield. Hydroxylation (71%) of 3 and methylation (77%) of the resulting hydroxypyridone 2 completed the first total synthesis of (+/-)-leporin A (1).     

Total synthesis of (+/-)-2-O-methylneovibsanin H

The total synthesis of (+/-)-2- O-methylneovibsanin H was achieved in 12 steps. An acid-catalyzed, one-pot, four-step cascade reaction was key to the concise total synthesis, lending support to the proposed biosynthesis.     

Total synthesis of (+/-)-symbioimine

The synthesis of (+/-)-symbioimine (1) has been completed in only 12 linear steps in 8% overall yield. The key step is the treatment of 13b with BF3.Et2O to generate N-carboalkoxydihydropyridinium cation 14b, which undergoes a novel stereospecific intramolecular Diels-Alder reaction to give adduct 16b in 42% yield. Cleavage of the N-Troc group of 16b afforded imine 24b stereospecifically. Cleavage of the TBDMS ethers and sulfation provided (+/-)-symbioimine (1). [reaction: see text].     

Remarkable control of radical cyclization processes of cyclic enyne: total syntheses of (+/-)-methyl gummiferolate, (+/-)-methyl 7beta-hydroxykaurenoate, and (+/-)-methyl 7-oxokaurenoate and formal synthesis of (+/-)-gibberellin a(12) from a common synthetic precursor.

Total syntheses of (+/-)-methyl gummiferolate (13b), (+/-)-methyl 7beta-hydroxykaurenoate (14b), and (+/-)-methyl 7-oxokaurenoate (14d) and a formal synthesis of (+/-)-gibberellin A(12) (15) have been accomplished through the common synthetic precursor, (3aR,7aR)-3,3-dimethyl-7a-(2-propynyl)-3a,4,7,7a-tetrahydroisobenzofuranone (16). The homoallyl-homoallyl radical rearrangement reaction of the monocyclic enyne 25, derived from 16 in two steps, afforded the bicyclo[2.2.2]octane compound 26, which was converted to (+/-)-methyl gummiferolate (13b). In contrast, the radical cyclization of the bicyclic enyne 16 gave the tricyclic lactone 19, leading to (+/-)-methyl 7beta-hydroxykaurenoate (14b) and (+/-)-methyl 7-oxokaurenoate (14d). Transformation of 14d into lactone 20 was carried out in a single step under bromination conditions. This constitutes a formal total synthesis of gibberellin A(12) (15).     

General and efficient strategy for erythrinan and homoerythrinan alkaloids: syntheses of (+/-)-3-demethoxyerythratidinone and (+/-)-erysotramidine

[reaction: see text] A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides followed by a N-acyliminium ion promoted intramolecular cyclization, and represents one of the shortest routes to erythrinan and homoerythrinan alkaloids. As the application, the formal total synthesis of (+/-)-3-demethoxyerythratidinone and the total synthesis of (+/-)-erysotramidine have been achieved, respectively.     

A formal total synthesis of (+/-)-halichlorine and (+/-)-pinnaic acid

[reaction: see text] A stereocontrolled approach for the preparation of the Danishefsky intermediates has been developed starting with the azaspirobicyclic ketone as a common precursor, representing a formal total synthesis of (+/-)-halichlorine and (+/-)-pinnaic acid. This approach involves the construction of the 1,7-disubstituted 6-azaspiro[4.5]decane with the proper stereochemistry established by olefin hydrogenation followed by C-methylation of the spirotricyclic lactam and the subsequent processes involving lactam ring-opening using methyl triflate and RCM to form the azaspirotricyclic quinolizidine skeleton.     

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide and approaches to the syntheses of (+/-)-6-epi-, (+/-)-15-epi-, and (+/-)-6,15-bisepidysidiolide

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide (1), a structurally novel sponge metabolite that inhibits the cdc25A protein phosphatase, and approaches to the syntheses of (+/-)-15-epi- (34), (+/-)-6-epi- (36), and (+/-)-6, 15-bisepidysidiolide (39) are described.     

General route to 4a-methylhydrofluorene diterpenoids: total syntheses of (+/-)-taiwaniaquinones d and h, (+/-)-taiwaniaquinol B, (+/-)-dichroanal B, and (+/-)-dichroanone

A general and convergent route for the synthesis of the 4a-methylhydrofluorene diterpenoids has been established through a common hexahydrofluorenone intermediate (10) obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane (13). The strategy has been successfully utilized for the synthesis of (+/-)-taiwaniaquinones D (3) and H (5), (+/-)-taiwaniaquinol B (1), (+/-)-dichroanal B (7), and (+/-)-dichroanone (8).     

Total synthesis of (+/-)-cameroonanol

[reaction: see text]The structure and relative stereochemistry of the novel silphiperfolane-type sesquiterpene cameroonan-7alpha-ol (1) were confirmed by a total synthesis of (+/-)-1 from 3,3,5-trimethylbicyclo[3.3.0]oct-1(8)-en-2-one (6) by means of a Sakurai reaction with (Z)-crotylsilane, free radical hydrobromination, base-induced cyclization, and LiAlH4 reduction.     

Total synthesis of (+/-)-spiroxin C

[reaction: see text] The first total synthesis of a marine-derived potent antitumor antibiotic, (+/-)-spiroxin C, was achieved via a TBAF-activated Suzuki-Miyaura cross-coupling reaction as a key step, which was also shown to be useful for the synthesis of sterically hindered binaphthyl derivatives.     

Total synthesis of (+/-)-momilactone A

The first total synthesis of (+/-)-momilactone A was accomplished using a highly diastereoselective transannular Diels-Alder reaction on a trans-trans-cis macrocyclic triene.     

Synthesis of (+/-)-5-epi-citreoviral and (+/-)-citreoviral and the kinetic resolution of an allylic silane by a [3 + 2] annulation

[reaction: see text] The [3 + 2] annulation reaction of allylsilane 1 with an alpha-keto ester provided the highly substituted tetrahydrofuran 2 as a single diastereomer in high yield. The synthesis of (+/-)-5-epi-citreoviral and (+/-)-citreoviral has been accomplished with this annulation reaction as the key step. Using the pantolactone-derived alpha-keto ester, the allylsilane 1 has been resolved with high enantiomeric purity.     

Total synthesis of (+/-)-8alpha-hydroxystreptazolone

[reaction: see text] The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable pentynyl appendage exclusively gave the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-en-7,10-diones. Based on this newly developed Pauson-Khand reaction of 2-oxazolone-alkyne derivatives, the first total synthesis of (+/-)-8alpha-hydroxystreptazolone was accomplished in a highly stereoselective manner.