Asymmetric synthesis of the core structure of (-)-CP-263,114

The enantioselective construction of a fully functionalized core structure of (-)-CP-263,114 (1), containing most of the required functionality for total synthesis, was conducted through sequential radical fragmentation-reductive olefination.     

An expeditious approach toward the total synthesis of CP-263,114

[reaction: see text] Assembly of the carbocyclic core of CP-263,114 has been accomplished efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and the late-stage fragmentation of a densely functionalized isotwistane skeleton.     

Studies in marine polypropionate synthesis: total synthesis of (-)-baconipyrone C

[reaction--see text] An asymmetric total synthesis of the unusual siphonariid metabolite, (-)-baconipyrone C (3), is described. Key steps included a tin(II)-mediated aldol coupling for the preparation of the carboxylic acid 17 and two different boron-mediated aldol additions leading to alcohol 8. Ester formation using modified Yamaguchi conditions gave 24, leading on PMB deprotection to (-)-baconipyrone C.     

Studies on the total synthesis of streptazolin and its related natural products: first total synthesis of (+/-)-8alpha-hydroxystreptazolone

The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable heptynyl appendage gave exclusively the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-ene-7,10-diones. On the basis of 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. In addition, (+/-)-7-epi-8alpha-hydroxystreptazolone was also synthesized.     

Concise total synthesis of (-)-mersicarpine

A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.     

Enantioselective total synthesis of (-)-laurenditerpenol

A highly convergent total synthesis of (-)-laurenditerpenol has been accomplished through an organolithium to aldehyde nucleophilic addition. Preparation of the prerequisite key intermediates in optically pure form was based on an improved, short, and efficient synthesis of "wine lactone" from (S)-limonene and Corey's catalytic enantioselective Diels-Alder reaction of 2,5-dimethyl furan with diethyl fumarate.     

Efficient total synthesis of (-)-stemoamide

An efficient diastereoselective synthesis of (-)-stemoamide has been accomplished from a pyroglutamic acid derivative in eight steps and with 24% overall yield. The synthesis features an intramolecular samarium diiodide-promoted 7-exo-trig cyclization of a ketyl radical generated from the corresponding aldehyde.     

Enantioselective total synthesis of (-)-dactylolide

[reaction: see text] The enantioselective total synthesis of (-)-dactylolide is reported. The absolute stereochemistry of the tetrahydropyran was established by catalytic asymmetric Jacobsen hetero-Diels-Alder reaction. The remote C19 stereocenter was introduced by a sequence of chelation-controlled Grignard addition and Ireland-Claisen rearrangement.     

Stereoselective total synthesis of (-)-kumausallene

A stereoselective total synthesis of (-)-kumausallene was completed in 12 steps from acetylacetone. The hidden symmetry of (-)-kumausallene was recognized, and its skeleton was constructed efficiently from a C(2)-symmetric diol by a palladium-catalyzed cascade reaction. High diastereoselectivity was observed for the DMF-promoted biomimetic 1,4-bromocyclization of a conjugated enyne.     

Asymmetric total synthesis of (-)-quinocarcin

(-)-Quinocarcin (1) has been synthesized in a longest linear sequence of 22 steps from 3-hydroxybenzaldehyde in 16% overall yield. The Pictet-Spengler reaction of L-tert-butyl-2-bromo-5-hydroxy phenylalanate (17), synthesized according to Corey-Lygo's enantioselective alkylation process, with benzoxyacetaldehyde (12) under mild acidic conditions afforded 1,3-cis tetrahydroisoquinoline 20 as an only isolable stereomer in 91% yield. The diazabicycle[3,2,1]-octane ring system of 28 was constructed by a silver tetrafluoroborate-promoted intramolecular Mannich reaction using amino thioether as a latent N-acyliminium species and tethered silyl enol ether as a nucleophile. Using amino thioether instead of aminal as a precursor of N-acyliminium was of high importance to the success of this otherwise disfavored 5-endo-Trig cyclization. A Hf(OTf)4-catalyzed (0.1 equiv) transformation of aminal to amino thioether was uncovered in the course of this study, allowing the conversion of tricyclic aminal 24 to amino thioether 25 to be realized in high yield. From the bridged tetracyclic compound 28, a sequence of oxidation of aldehyde to acid, global deprotection under hydrogenolysis conditions, and one-pot partial reduction of lactam to aminal/oxazolidine formation completed the total synthesis of the pentacyclic (-)-quinocarcine.     

Asymmetric total synthesis of (-)-mycothiazole

[structure: see text] In this Letter we describe the first total synthesis of mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary alcohol. The skipped diene was constructed by the standard Stille coupling, and the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille coupling.     

Formal total synthesis of (-)-lepadiformine

[reaction: see text] A stereocontrolled approach to the preparation of the Weinreb intermediate 3 has been developed. The important features of this approach are the creation of stereogenic centers through a cyclic amino acid ester-enolate Claisen rearrangement and the use of ring-closing metathesis for the construction of the azaspirocyclic skeleton.     

Enantiospecific total synthesis of (-)-4-thiocyanatoneopupukeanane

Enantiospecific synthesis of the natural enantiomer of the marine sesquiterpene (-)-4-thiocyanatoneopupukeanane (6) is described. The bicyclo[2.2.2]octanecarboxylate 14, obtained from (R)-carvone via Michael-Michael reaction, was transformed into neopupukeananedione 12 by employing rhodium acetate catalyzed intramolecular C-H insertion of the diazo ketones 16 or 19 as the key reaction. Regioselective deoxygenation of the C-2 ketone transformed the dione 12 into neopupukean-4-one 10. Alternately, the keto ester 18 was also transformed into neopupukean-4-one 10 via regioselective deoxygenation of the ketone in 18 followed by intramolecular rhodium carbenoid C-H insertion of the diazo ketone 31. Finally, neopupukean-4-one 10 was transformed into (-)-4-thiocyanatoneopupukeanane 6 via the alcohol 32 and the mesylate 33.     

Concise total synthesis of (-)-8-epigrosheimin

A highly efficient route was developed to synthesize (-)-8-epigrosheimin in four steps from aldehyde 2 based on a substrate-controlled method. The key steps of the synthesis included (1) a stereo- and regioselective allylation addition, (2) an intramolecular translactonization, and (3) an aldehyde-ene cyclization.     

Study of the total synthesis of (-)-exiguolide

In this article, we disclose the various routes and strategies we had to explore before finally achieving the total synthesis of (-)-exiguolide ((-)-1). Two first types of approaches were set, both relying on the Trost's domino ene-yne coupling/oxa-Michael reaction that we choose for its ability to control the geometry of the methylacrylate-bearing tetrahydropyrane ring B. In our first approach, we expected to assemble the two main fragments (C14-C21 and C1-C13) by creating the C13-C14 bond through a palladium(0)-catalyzed cross-coupling, but this step failed, unfortunately. In the second approach, which was more linear, we created the C16-C17 bond through condensation of a lithium acetylide on a Weinreb amide, and we assembled the C1-C5 and C6-C21 subunits through Trost's domino ene-yne coupling/oxa-Michael reaction. These two approaches served us to design an ameliorated third strategy, which finally led to the total synthesis of (-)-exiguolide.