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A convergent and efficient approach towards the total synthesis of Kadcotrione B is described. For this purpose, the syntheses of two fragments, 6/6/5-fused tricyclic ring and C-9 side chain, were accomplished. The salient features of these syntheses are the utilization of aldol condensation, Evans aldol reaction, Horner–Wadsworth–Emmons olefination, Michael addition, Robinson annulation, and Wacker oxidation.

A general approach for a collective synthesis of natural products containing substituted THF ring is described. In this paper, Arbusculone, a small molecule natural product accomplished using a short route, is used as the key intermediate to achieve the total synthesis of Andirolactone, Pinnatolide, Ipomolactone, Cyclocapitelline, Isocyclocapitelline and their two isomers in less than ten steps. The present effort highlights protecting-group-free total syntheses and the shortest route to access these natural products from commercially available cheap starting materials.

We have developed a facile and efficient synthetic route to substituted isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a variety of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive free and takes place at reflux conditions with short reaction time to furnish products in good to excellent yields. All the compounds have been characterized by spectral techniques such as IR, 1H NMR and Mass etc. Synthesized compounds were evaluated for antimicrobial activity against specific bacterial like 1) Staphylococcus strains aureus 2) Bacillus subtilis 3) Escherichia coli 4) Pseudomonas aeruginosa. Compounds 3e, 3n, 3 m, 3 l, 3 k, 3j and 3b showed most potent in vitro activity against bacterial strains.

An efficient and stereoselective approach for the formal total synthesis of Stigmatellin A has been described. The key steps involved in this synthesis are desymmetrization of the bicyclic olefin to introduce two methyl and two hydroxyl chiral centers, Friedel Crafts acylation, regioselective demethylation, Baker-Venkataraman rearrangement and Grubbs cross metathesis.

The first asymmetric total synthesis of the putative structure of diplopyrone was achieved in 17 linear steps starting from cis-1,4-butene-diol. The synthetic route features iodine-catalyzed tandem isomerization followed by C–O and C–C bond formation reaction strategy developed by our own group to construct the trans-2,6-disubstituted dihydropyran ring, asymmetric α-aminoxylation reaction, and Still–Gennari (Z)-selective olefination reactions. Careful comparison of 1H and 13C NMR spectroscopic data as well as investigation of the UV and circular dichroism spectrum in trifluoroethanol for compound 2 suggest that the putative structure for diplopyrone {6-[(1S)-1-hydroxyethyl]-2,4a(S),6(R),8a(S)-tetrahydropyran[3,2-b]pyran-2-one} requires revision.

A series of novel 1,2,3-triazole and isoxazole-linked pyrazole derivatives have been synthesized from pyrazole and triazole/isoxazole scaffolds. The synthesized congeners were evaluated for their anti-proliferative efficacy in four cancer cell lines (MCF7, HEPG2, IMR32, and HELA). Majority of the compounds demonstrated potent cytotoxic activities, among them 4k and 4l showed significant cytotoxicity in all the tested cell lines.

The first total syntheses of two possible diastereomers of gliomasolide E, a 14-membered macrolides isolated from the marine sponge Phakellia fusca Thiele, which was collected from the South China Sea, is reported. Highlights of the synthesis include macrolactonization through intramolecular Horner–Wadsworth–Emmons olefination, Yamaguchi–Hirao alkynylation, and base-induced elimination reactions for propargyl alcohol synthesis as the key reactions. Detailed comparison of their 1H and 13C NMR (1D and 2D NMR data) and specific rotation with those of the natural product revealed that the absolute stereochemistry of gliomasolide E should be (2E,5R,7R,9R,13R).

A first stereoselective total synthesis of 14-memebered β-resorcylic macrolactone 5′-hydroxyzearalenone (1) has been achieved. The key steps are Jocobsen hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylation, Vilsmeier-Haack reaction, Mitsunobu esterification and ring-closing metathesis.

Total synthesis of spiroketal EBC-23 has been described by two divergent approaches from three simple building blocks. Gold-catalyzed cycloisomerization of alkynol and acid-mediated spirocyclization of diketalketone were successfully utilized to effect spiroketal formation. A Cu(I)-P(Cy)3-catalyzed protocol for the highly regio- and stereocontrolled hydroboration of internal propargylic alcohol was effectively applied toward the β-hydroxy ketone via vinylboronates.

A highly stereoselective formal total synthesis of brevisamide is described that proceeds through a convergent pathway and utilizes our own tandem isomerization/C–O and C–C bond formation reaction as the key step to construct the trans-2,6-disubstituted dihydropyran ring system. Other significant reactions in this synthesis include an iodolactonization, a Crimmins-modified “non-Evans” syn aldol reaction, and a Horner–Wadsworth–Emmons olefination.

A highly stereoselective total synthesis of the diacetonide derivative of the antibiotic thuggacin A has been described. The synthesis features the stereoselective Stille cross-coupling reaction to set up the whole carbon framework, aldol condensation to construct the highly substituted conjugated diene, non-Evans syn aldol, CBS reduction, Hantzsch's thiazole synthesis, Horner-Wadsworth-Emmons reaction, and Shiina's macrolactonization.

Various aldehydes undergo a smooth cascade cyclization with N-(5-hydroxypent-2-yn-1-yl)-4-methyl-N-phenylbenzenesulfonamide in the presence of 10 mol% Ph3PAuCl/AgSbF6/In(OTf)3 to furnish the corresponding tetrahydro-2H-pyrano[3,4-c]quinoline derivatives in good yields with high selectivity. This is the first report on the synthesis of tetrahydro-2H-pyrano[3,4-c]quinolines through a tandem hydroarylation/Prins cyclization process.

The first stereoselective total synthesis of nonenolide (−)-stagonolide D has been accomplished. Midland Alpine borane reduction to install hydroxyl group at C4, Henbest epoxidation to introduce epoxide stereoselectively between C7 and C8, Yamaguchi esterification and Olefin metathesis reaction are the key steps involved in the total synthesis.

An intramolecular annulation strategy has been developed for the synthesis of tetrahydrobenzo[e]pyrano[4,3-c][1,2]thiazine derivatives by means of coupling of aldehydes with 2-(4-hydroxybut-1-yn-1-yl)-N-arylsulfonamides using a catalytic amount of silver hexafluoroantimonate in toluene at 80 °C. This is the first report on the synthesis of fused benzo-δ-sultam derivatives through C–N, C–O, and C–C bond formations. The reaction proceeds through a cascade of hydroamination and Prins type cyclization.

A convergent and stereoselective approach for the synthesis of C1–C23 and C24–C32 segments of polyether antibiotic, ionomycin has been achieved. The key steps involved in this approach are the elaboration of two advanced fragments from a common precursor using enzymatic desymmetrization to create two methyl chiral centers, desymmetrization of the bicyclic olefin to introduce two methyl and two hydroxyl chiral centers, the use of Evans auxiliary to introduce another methyl group and the creation of four chiral centers in bis -tetrahydrofuran ring by Sharpless asymmetric epoxidation and the regioselective opening of epoxide with methyl sulphone. The coupling of C11–C16 with C17–C23 was achieved through a Julia-Kocienski olefination and directed Aldol reaction. Oxidation of C9 alcohol facilitates the coupling of C10–C23 with C1–C9.

A domino cyclization of 3-((3-(2-aminophenyl)prop-2-ynylamino)methyl)but-3-en-1-ol with aldehydes has been accomplished employing 5 mol % of the Ph3PAuCl/AgSbF6/In(OTf)3 system to afford the corresponding octahydrospiro[pyran-4,4'-pyrido[3,4-b]indole] derivatives in good yields with high selectivity. This is the first report on the synthesis of spiro-β-carbolines through a multicatalytic cascade process.

A straightforward synthesis of (S)-gingerols 1–3 has been described. The requisite stereogenic center in the target molecules was introduced by Sharpless asymmetric dihydroxylation using a chiral complex, AD-mix β. This route is simple and efficient to prepare the products in very good yields.

A unified synthetic strategy has been developed for the total synthesis of the dendrodolide family, employing Jorgensen asymmetric epoxidation, Keck allylation, Brown allylation, Yamaguchi esterification, and ring-closing metathesis as key reactions.

A convergent total synthesis of isocladosporin and 3- epi -isocladosporin is reported starting from commercially available homoallyl alcohol in 10 longest linear steps with 28% overall yield. The key steps involved in the synthesis are cross-metathesis, tandem isomerization followed by C O and C C bond formation reactions for the synthesis of trans -2,6-disubstituted dihydropyrans developed by us, acylation reaction and Luche reaction.

A stereoselective synthesis of tetrahydropyran–tetrahydrofuran (THP–THF) core 2 of (+)-muconin (1) has been achieved using Prins cyclization as a key step to construct tetrahydropyran moiety. Other important transformations such as Wittig olefination, Sharpless epoxidation, regio-, and stereoselective exo-cyclization of the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy alcohol, Grignard reaction, and Barton–McCombie reaction are successfully employed to accomplish the synthesis of THP–THF core 2.

A tandem gold-catalyzed 5-endo-dig/spirocyclization of 2-[(2-aminophenyl)ethynyl]phenylamines with isatins was achieved to produce the corresponding 5′,11′-dihydrospiro[indoline-3,6′-indolo[3,2-c]quinolin]-2-one derivatives in good yields with high regioselectivity. This reaction proceeded well at ambient temperature under mild conditions. Ketones also participated smoothly under similar conditions to produce 6,6-disubstituted-6,11-dihydro-5H-indolo[3,2-c]quinolones.

Stereoselective synthesis of the C21–C40 core segment of caylobolide A has been achieved following a highly efficient convergent strategy. The key reactions featured in the synthesis are Prins cyclization, reductive radical cyclization, Sharpless asymmetric epoxidation and olefin cross metathesis.

The stereoselective synthesis of C1-C17 fragment of salinomycin is achieved. The strategy employs a desymmetrization approach and utilizes an intramolecular oxetane opening reaction with O-nucleophile to result in the tetrahydropyran skeleton as the key step.

A stereoselective total synthesis of phomolides G and H, a polyketide natural products is described. The synthesis involves organocatalytic enantioselective asymmetric epoxidation, C1-Wittig olefination, and ring-closing metathesis as key steps. The use of organocatalytic MacMillan asymmetric epoxidation for the construction of two chiral centers of phomolides G and H makes this approach more attractive.

Stereoselective synthesis of the naturally occurring 6-membered lactone hyptolide 1 is described. The main feature of the synthesis is the utility of the hitherto unexplored alkyne fragment derived from commercially available 3-butyn-1-ol (homopropargylic alcohol).

A highly efficient asymmetric cascade reaction namely Michael-hemiketalization of 5-hydroxy-2-methyl-4H-pyran-4one to β,γ-unsaturated α-ketoesters has been developed using a chiral bifunctional rosin–indane amine thiourea catalyst. The products are obtained in excellent yields with a high degree of enantiomeric excess (up to 99% ee), in a short reaction time with low catalyst loading of 2.5 mol%.

Pd/Mg–La mixed oxide is used as an efficient catalyst for the oxidative direct acylation of arene sp2 C H bonds with alcohols. TBHP was used for in situ oxidation of the alcohols to aldehydes which after coupling with 2-aryl pyridines forms aryl ketones. The catalyst is recovered and used for four cycles.

The synthesis of phomopsolide B has been achieved using an olefin cross-metathesis (CM) reaction as key step. Two metathesis partners, enediol and 5-hydroxy vinyl lactone were prepared from l -ascorbic acid. This is the first report of using 5-hydroxy vinyl lactone in an olefin cross-metathesis reaction.

An asymmetric synthesis of spiroketal fragment of an antitumour antibiotic, ossamycin is described. Coupling of aldehyde and alkyne fragments followed by spiroketalization has afforded the spiroketal sub unit of ossamycin. Both the sub targets were constructed via Prins cyclization.

A concise approach for the total synthesis of attenols A and B is described involving MacMillan’s α-aminooxylation, Evan’s asymmetric alkylation, Brown’s allylation, and spiro-ketalization as key steps. This approach has successfully demonstrated the α-aminooxylation protocol for the construction of the anti-1,3-diol unit.

The stereoselective total synthesis of (−)-brevisamide, a novel marine cyclic ether alkaloid isolated from dinoflagellate karenia brevis is described. The key steps involved in this synthesis are the Sharpless asymmetric epoxidation and regioselective ring opening of chiral epoxide by Gilman's reagent. The tetrahydropyran core has been constructed by an intramolecular SN2 cyclisation.

2-Amino-5-hydroxypropiophenone, a key precursor in the total synthesis of irinotecan, has been synthesized. Regioselective nitration and a SNAr displacement are the key steps involved in this strategy, which is high yielding, is economical, and has been performed on a plant scale. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

A flexible and highly diastereoselective formal synthesis of hapalosin, a cyclodepsipeptide isolated from the blue green alga Hapalosiphon welwitschii and having multidrug-resistance-reversing activity is described. The synthetic route involves the addition of organometallic reagent to N-tert-butanesulfinylimine, Jung nonaldol aldol reaction, and Yamaguchi esterification as key steps.

A novel thia-Prins bicyclization approach has been developed for the first time for the synthesis of hexahydro-2H-thieno[3,2-c]thiopyran derivatives from the coupling of homoallylic mercaptans such as hex-3-ene-1,6-dithiol with various aldehydes using 10 mol % InBr3 in dichloromethane with high selectivity. In addition, the coupling of (E)-N-(6-mercaptohex-3-enyl)-4-methylbenzenesulfonamide with aldedydes affords the corresponding N-tosyloctahydrothiopyrano[4,3-b]pyrrole derivatives in good yields. This reaction is a stereoselective affording trans-fused product from E-homoallyllic mercaptan and cis-fused product from Z-homoallyllic mercaptan.

A bioglycerol derived carbon-sulfonic acid is found to catalyze efficiently the three-component one-pot condensation of isatin, malononitrile, and 1,3-dicarbonyls to afford a wide range of spiro[4H-pyran-3,3′-oxindole]derivatives in good yields and selectivity. The use of a recyclable solid acid catalyst makes this method simple, convenient, and cost-effective.

The asymmetric and convergent synthesis of fully functionalized macrocyclic core of tulearin C is described. Sharpless asymmetric epoxidation, Gillman’s reaction, olefin cross metathesis, α aminoxylation, and ring closing metathesis reactions are the key steps utilized in the synthesis of macrolactone.

A stereoselective synthesis of the spirolactam fragment (C31–C41) of a highly-potent immunosuppressant sanglifehrin A is described. The key steps involved in this synthesis are a desymmetrization protocol, Sharpless asymmetric epoxidation, Crimmins syn aldol reaction, Barton–McCombie deoxygenation, and acid-mediated spirolactamization.

A novel Prins/Friedel–Crafts cyclization of ( Z )-6-(1-methyl-1 H -indol-3-yl)hex-3-en-1-ol with aldehydes has been achieved using a catalytic amount of BF 3 ·OEt 2 under mild reaction conditions to produce the corresponding octahydropyrano[4,3- a ]carbazole derivatives in good yields with high diastereoselectivity. The cross-coupling of ( Z )-6-(1-methyl-1 H -indol-3-yl)hex-3-ene-1-thiol with aldehydes affords the corresponding octahydrothiopyrano[4,3- a ]carbazole derivatives under similar conditions.

Three components coupling of alkyl bromide, sodium azide and alkyne has been achieved using a catalytic amount of copper-exchanged phosphotungstic acid (Cu-TPA) in the presence of triethyl amine in DMF to afford substituted triazoles in good yields with high selectivity. Interestingly, the coupling of alkyl azide with alkyne proceeds readily at room temperature to furnish 1,2,3-triazoles in excellent yields. The catalyst can be recovered and reused for three to four subsequent runs with a minimal decrease of activity. The use of copper modified heteropolyacids makes this procedure simple, convenient and environmentally friendly.

The homoallylic alcohol tethered with a benzylic hydroxyl group, that is, ( E )-4-(2-(hydroxymethyl)phenyl)but-3-en-1-ol undergoes smooth Prins bicyclization with various aldehydes in the presence of 20 mol % Sc(OTf) 3 and 4 A MS at 80 °C to afford a novel series of 1-(tetrahydrofuran-3-yl)-1,3-dihydroisobenzofuran derivatives in good yields with high diastereoselectivity.

2-Arylethylbut-3-en-1-ol is found to undergo smooth Prins cascade reactions with various aldehydes in the presence of Sc(OTf)3 (10 mol-%) and a stoichiometric amount of TsOH to afford the corresponding trans-fused hexahydro-1H-benzo[f]isochromenes in good yields with excellent selectivity. Likewise, N-tosyl-2-phenethylbut-3-en-1-amine gives trans-fused octahydrobenzo[f]isoquinoline derivatives under similar conditions. This is the first example of the synthesis of hexahydro-1H-benzo[f]isochromene and octahydrobenzo-[f]isoquinoline from 2-arylethylbut-3-en-1-ol and N-tosyl-2-phenethylbut-3-en-1-amine, respectively.

A novel method has been devised for the synthesis of 2,4,5-trisubstituted pyrrole derivatives through the coupling of α-diazoketones with β-enaminoketones and esters using 10 mol % of Cu(OTf)(2). A wide range of 2,3-disubstituted indole derivatives were also prepared from α-diazoketones and 2-aminoaryl or alkyl ketones. The synthetic versatility of this approach has been exemplified in the formal synthesis of homofascaplysin C.

A domino cycloisomerization/Pictet-Spengler reaction of 2-(4-aminobut-1-yn-1-yl)aniline with aldehydes has been achieved using a AuIPrCl (5 mol %)/AgSbF(6) (10 mol %) catalytic system to produce the corresponding 1-aryl-N-tosyl-2,3,4,5-tetrahydropyrido[4,3-b] indole derivatives in good yields. This is the first report on the synthesis of tetrahydro pyrido[4,3-b]indole scaffolds through as tandem 5-endo-dig cyclization and Pictect-Spengler reaction.

The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Other key steps involve an allene-type rearrangement or enyne isomerization to install the triene moiety, a Seebach methylation, a Julia olefination to construct the trisubstituted diene unit, and an enzymatic resolution strategy to generate the C-18 stereocenter.

The stereoselective synthesis of C1–C10 fragment of cytostatic macrolide bryostatin is described. Two of the three chiral centers have been established via the Sharpless kinetic resolution of racemic allylic alcohol 15 followed by regioselective reduction of epoxy alcohol 8 with Red-Al. Diastereoselective Aldol reaction of an aldehyde 7 with methyl isobutyrate affords the corresponding β-hydroxyester 23 which is then transformed into tetrahydropyran ring system 3 via an intramolecular hemi-ketalization.