A convergent synthesis of the tricyclic architecture of the guanacastepenes featuring a selective ring fragmentation

[reaction: see text] This Letter describes a concise, diastereoselective synthesis of the tricyclic carbon framework of the guanacastepene family of natural products. An intermolecular Diels-Alder reaction established a remote stereochemical relationship and facilitated a synthesis of allylic acetate 3, which was subsequently joined with vinylstananne 9 via a Stille coupling. An intramolecular [2 + 2] photocycloaddition then afforded complex cyclobutyl ketone 19, which underwent a stereoelectronically controlled fragmentation to the guanacastepene architecture on treatment with samarium diiodide.     

Synthetic approaches to guanacastepenes. Enantiospecific syntheses of BC and AB ring systems of guanacastepenes and rameswaralide

[reaction: see text] A simple and efficient approach for the BC and AB ring systems of the novel diterpenes guanacastepenes and rameswaralide starting from the readily and abundantly available monoterpene (R)-carvone employing RCM reaction as the key step is described.     

The enantioselective syntheses of bisabolane sesquiterpenes Lepistirone and Cheimonophyllon E

The synthetic approach to the bisabolane sesquiterpenes Lepistirone 1 and Cheimonophyllon E 2 involves the transformation of (+)-2-carene (5) into the p-menthane furans 8 and 11. Regio- and stereoselective alkylation, and standard reactions complete the enantioselective syntheses.     

Convergent and enantioselective syntheses of both enantiomers of (5Z)-tetradecen-4-olide,scarab beetle pheromones

Japonilure and its enantiomer, that is, (R)-(−)- and (S)-(+)-(5Z)-tetradecen-4-olide, have been synthesised in satisfactory overall yields using a highly convergent procedure. In situ prepared 1-decynylethylzinc was enantioselectively coupled to isopropyl 4-oxobutanoate in the presence of (S)- or (R)-BINOL. The alkoxy-ester intermediates obtained were cyclised to the corresponding substituted γ-lactones, carrying a triple bond in the side chain. Lindlar-hydrogenation of the latter yielded the target compounds.     

Convergent enantioselective syntheses of two potential C25-C40 subunits of (−)-caylobolide A

The convergent syntheses of two possible diastereomers of the C25-C40 subunit resident in (−)-caylobolide A have been accomplished. The key reaction featured a chemoselective Ru-catalyzed cross-metathesis between a fully elaborated type I and two functionalized type II α,β-unsaturated ketones.     

Convergent syntheses of luteoreticulin and didemethylluteoreticulin

Convergent syntheses of luteoreticulin (1a) and didemethylluteoreticulin (1c) are described which are ammenable to structural variation in both the pyran and phenyl rings.     

Simple, catalytic enantioselective syntheses of estrone and desogestrel

Highly enantioselective and very short syntheses of the bioactive forms of estrone (3) and desogestrel (4) are described using a chiral oxazaborolidinium catalyst (2) in the key initial step. Enantiomerically pure estrone was synthesized in eight steps from the readily available starting materials diene 5 and alpha,beta-enal 6 via intermediates 8 and 9. Desogestrel was synthesized using a similar strategy from diene 5 and alpha,beta-enal 11 via intermediates 12-17. The efficient syntheses of the chiral catalyst 2 and its enantiomer are also presented.     

Efficient and enantioselective total syntheses of heliannuols A and K

The second-generation enantioselective synthesis of heliannuol A and the first enantioselective total synthesis of heliannuol K (via two routes) have both been accomplished efficiently; (heliannuol A, nine steps and 25% yield; heliannuol K, seven steps and 47% yield). Highlights of our synthetic strategy include a substrate-controlled chirality transfer in the Lewis acid mediated Claisen rearrangement of the allyl aryl ether for the key construction of a tertiary stereogenic center at the benzylic position followed by, for heliannuol A, ring-closing metathesis, diastereoselective epoxidation, and regioselective cleavage of the epoxide; and for heliannuol K, ring-closing metathesis and conjugate reduction of the eight-membered enone.     

Total syntheses of furaquinocin A, B, and E

A modular approach to the total synthesis of furaquinocins culminated in the total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck cyclization allows the enantio- and diastereoselective construction of dihydrobenzofuran 32. Introduction of a double unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the naphthoquinone with squaric acid based methodology leads to furaquinocin E. The use of differentially substituted squaric acid derivatives allows the synthesis of three analogues of furaquinocin E. The additional stereocenters in furaquinocin A and B can be introduced with a diastereoselective Sakurai allylation. The stereoselective elongation of the side chain is possible using cross metathesis or ring closing metathesis. The obtained late-stage intermediates were successfully transformed to furaquinocin A and B.     

Convergent enantioselective synthesis of the tricyclic core of phomactin A

[reaction: see text] The tricyclic core of phomactin A was synthesized from 6,6-dimethyl-2-cyclohexen-1-one. Key reactions include the addition of a cyclohexenyllithium reagent to an epoxyaldehyde and a regioselective intramolecular epoxide opening to install the oxadecalin core.     

Concise syntheses of coronarin A, coronarin E, austrochaparol and pacovatinin A

Total syntheses of (+)-coronarin A (1), (+)-coronarin E (2), (+)-austrochaparol (3) and (+)-pacovatinin A (4) were achieved from the synthetic (+)-albicanyl acetate (6). Dess-Martin oxidation of (+)-albicanol (5) derived from the chemoenzymatic product (6) gave an aldehyde (7), which was subjected to Julia one-pot olefination using beta-furylmethyl-heteroaromatic sulfones (8 or 9 ) gave (+)-trans coronarin E (2) and (+)-cis coronarin E (12) with high cis-selectivity. The synthesis of (+)-coronarin A (1) from (+)-trans coronarin E (2) was achiev-ed, while (+)-cis coronarin E (12) was converted to the natural products (+)-(5S,9S,10S)-15,16-epoxy-8(17),13(16),14-labdatriene (13) and (+)-austrochaparol (3). By the asymmetric synthesis of (+)-3, the absolute structure of (+)-3 was determined to be 5S, 7R, 9R, 10S configurations. Homologation of (+)-albicanol (5) followed by allylic oxidation gave (7 alpha)-hydroxy nitrile (17), which was finally converted to the natural (+)-pacovatinin A (4) in 8 steps from (+)-albicanol (5).     

Studies toward the enantioselective syntheses of oxylipins: total synthesis and structure revision of solandelactone E

An efficient and general entry to unsaturated cyclopropane- and lactone-containing oxylipins of marine origin has been designed and applied to the first enantioselective total synthesis of solandelactone E. The synthesis, which proceeds in a total of 23 steps from commercially available materials, features a diastereoselective acetal-directed cyclopropanation of an electron-deficient diene, a regioselective Sharpless enantioselective dihydroxylation, and a stereoselective [2,3]-sigmatropic rearrangement of a selenoxide to effect a 1,3-transposition of an allylic alcohol. Comparison of spectral data for the synthetic solandelactone, thus prepared, with data in the literature led to a revision of the original structural assignments of the C(11)-epimeric solandelactones.     

Concise enantioselective syntheses of quinolactacins A and B through alternative Winterfeldt oxidation

Enantioselective total syntheses of (+)-quinolactacin B and (+)-quinolactacin A2 through asymmetric Pictet-Spengler cyclization and KO(2) oxidation-an alternative Winterfeldt condition-are described.     

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1]nonan-3-ones is presented.Using keto-lactams as the starting materials,this two-step method consists of silyl enol ether formation with TBDMSOTf,lactam activation with Tf2O/DTBMP,and halide-promoted cyclization.Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones,which can be hydrogenated to yield3,6-dihydroxytropanes.Starting from optically active keto-lactams,the method has been applied to the enantioselective syntheses of(+)-(1S,3S,5R,6S)-pervilleine C(6),(+)-(1S,3R,5S,6R)-valeroidine(3),(+)-(1S,3S,5R,6S)-dibenzoyloxytropane(8),and(+)-(1S,3S,5R,6S)-merredissine(9).     

Convergent, stereoselective syntheses of the glycosidase inhibitors broussonetines C, O and P

The first syntheses of the polyhydroxylated alkaloids (iminosugars) broussonetines O and P, glycosidase inhibitors of the pyrrolidine class, have been performed in a convergent, stereocontrolled way from d-serine as the chiral starting material. The synthesis of broussonetin C, a further member of this compound family, is also reported. A cross-metathesis step was one key feature of the synthesis. The versatility of the synthetic concept chosen permits the access to many members of this compound family, both natural ones and analogues thereof.     

A practical enantioselective total synthesis of the bengamides B,E, and Z

[reaction: see text] A practical total synthesis of Bengamides B, E, and Z from a common polyol intermediate is described. Consecutive aldol condensations afford a protected polyol thioester side chain suitable for coupling to the Bengamides. A novel chiral phase transfer catalyzed enantioselective alkylation affords the more highly functionalized amino caprolactams required for Bengamides B and Z. Use of the 2-naphthylmethyl ether protecting group, compatible with the boron Lewis acids required for enantioselective aldol condensation, allows direct access to Bengamide B.     

Convergent and enantioselective total synthesis of (−)-nalanthalide, a potential Kv1.3 blocking immunosuppressant

The first total synthesis of (−)-nalanthalide (1), a novel blocker of the voltage-gated potassium channel Kv1.3 from a microorganism, was accomplished in a convergent manner by utilizing coupling reaction of the trans-decalin 5 with 3-lithio-γ-pyrone 4. The key intermediate 5 was efficiently prepared from the known trans-decalone 7 through a [2,3]-Wittig rearrangement of the stannylmethyl ether 6 to install the stereogenic center at C9 and the exo-methylene function at C8.