Asymmetric total synthesis of spongistatins 1 and 2

The total synthesis of spongistatin 1 (1) and spongistatin 2 (2) has been achieved through an advanced-stage intermediate. The synthesis is highlighted by a highly convergent assembly of the four key fragments (the C1-C15 AB fragment 2, the C16-C28 CD fragment 3, the C29-C43 EF fragment 4, and the C44-C51 side chain 5) at a very advanced stage of the synthesis with minimal functional group interconversion. The CD fragment 3 functions as the central building block to which the other fragments are attached. The synthesis of the AB and CD spiroketal fragments is accomplished through the addition of a metalated gamma-pyrone to a beta-alkoxy aldehyde followed by spiroketalization. The EF subunit was assembled with high diastereoselectivity relying on asymmetric aldol reactions of chlorotitanium enolates of N-propionyl oxazolidinethiones and a double diastereoselective boron aldol to join the E and F fragments. Wittig coupling of the CD and EF fragments followed by a diastereoselective aldol reaction between the CDEF ketone and an AB aldehyde set the stage for attachment of the C44-C51 side chains and final macrolactonization and deprotection.     

Total synthesis and determination of the absolute configuration of coscinosulfate. A new selective inhibitor of Cdc25 protein phosphatase.

The first total synthesis of coscinosulfate 1, a metabolite isolated from a sea sponge, starting from (+)-sclareolide 3 is described. The convergent synthesis strategy relies on the coupling of sulfone 21 with the bromide 26. The sulfone fragment 21 was obtained by successive asymmetric aldol reaction with aldehyde 2 to introduce the stereocenters at C-12 and C-13, followed by one-carbon homologation via Horner-Wadsworth-Emmons olefination. The selective sulfatation at C-12 was accomplished through the quinone intermediate 31 obtained by selective oxidation of hydroquinone 30; this, when followed by reduction, furnished the desired coscinosulfate 1. X-ray analysis of the intermediate aldehyde 18 confirmed the proposed structure.     

Mixed organofluorine-organosilicon chemistry. 13. One-pot synthesis of difluoroaldols from acylsilanes and trifluoromethyltrimethylsilane. application to the synthesis of a difluoro analogue of egomaketone

Difluoroaldol compounds 3 were synthesized in a one-pot procedure involving an acylsilane 1, trifluoromethyltrimethylsilane (TFMTMS), and an aldehyde. The key intermediate of this reaction is a difluoroenoxysilane 2. Ytterbium triflate proved to be a very efficient catalyst for promoting the aldol type reaction under very mild conditions. The potential of this reaction for the convergent synthesis of difluorinated compounds was illustrated by the synthesis of difluoroegomaketone 7d through dehydration of the corresponding aldol compound 3d.     

Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised structure

The first total synthesis of jimenezin was achieved by using carbohydrates as chiral building blocks, thus revising the proposed structure 1 to 2. The key steps in this synthesis include an efficient construction of the THP-THF fragments 3 and 16 through a stereoselective condensation between the pyranyl aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling reaction of 3 or 16 with a terminal butenolide 4.     

One-Pot Three-Component Synthesis of 3-Aminoimidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridines and -pyrazines in the Presence of Silica Sulfuric Acid

Summary. The synthesis of 3-aminoimidazo[1,2-a]pyridines and 3-aminoimidazo[1,2-a]pyrazines through a condensation reaction of 2-aminopyridine or 2-aminopyrazine, aldehyde, and alkyl or aryl isocyanide in high yields at room temperature in the presence of silica sulfuric acid is described.     

Stereospecific nitromethane conjugate addition to 4-oxygenated-2-substituted-cyclo pent-2-enones: a simple approach to prostaglandins

The compatibility of nitromethane conjugate addition to 2-cyclo-pentenones bearing a 4-oxygenated function has been illustrated through a short and practical synthesis of the Corey aldehyde, a key intermediate in prostaglandin synthesis, in both racemic and optically active form. A new synthesis of PGF_2α featuring the introduction of the ω-chain via [3+2] cycloaddition has been also described.     

1,2-丙二醇合成丙酮醛反应催化剂的研究

通过固定床反应器考察了掺磷玻璃微珠银催化剂对１,２－丙二醇选择性氧化合成丙酮醛的催化性能。试验结果表明,在适宜的条件下,该催化剂对１,２－丙二醇的转化率达到９８％,对丙酮醛选择性达到了６９％。作者还就磷对催化剂选择性的提高给出了解释     

A concise total synthesis of (+/-)-1-epiaustraline

[reaction: see text] A concise total synthesis of 1-epiaustraline 3 is described that utilizes a diastereoselective Birch reduction of an electron-deficient pyrrole and a chelation-controlled vinyl Grignard addition to an aldehyde to introduce the C7 stereocenter. The C1 and C2 stereocenters were set through an OsO(4)-catalyzed dihydroxylation.     

Synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin: a formal total synthesis

The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.     

Synthesis of oligoenes that contain up to 15 double bonds from 1,6-heptadiynes

This paper reports the synthesis of polyene oligomers ("oligoenes") that contain up to 15 double bonds that are identical to the "all five-membered ring" species formed through cyclopolymerization of diisopropyldipropargylmalonate. The oligoenes contain an isopropylidene unit at each end. The isolated oligoenes range from the "dimer" (a pentaene, (E)-di-1,2-[1-(2-methyl-propenyl)-4,4-di-iso-propyl-carboxy-cyclopent-1-enyl]-ethene (3b2)) to the "heptamer" (3b7, a pentadecaene). Oligoenes 3b2, 3b3, 3b4, 3b5, and 3b7 were prepared through Wittig-like reactions between aldehydes and the appropriate monometallic Mo alkylidene or bimetallic Mo bisalkylidene species whose alkylidene is derived from an identical five-membered ring monomeric unit. Compounds 3b2, 3b4, and 3b6 were prepared through McMurry coupling reactions of aldehydes. A representative aldehyde (the "monomeric" aldehyde) is diisopropyl-3-formyl-4-(2-methylprop-1-enyl)cyclopent-3-ene-1,1-dicarboxylate (2b), McMurry coupling of which yields 3b2. A heptaene that contains a six-membered ring in the central unit also was prepared in a Wittig-like reaction involving a bimetallic Mo alkylidene; this species is a model for oligoenes that contain both six-membered and five-membered rings. X-ray structures of two bimetallic species that are employed in the synthesis of the oligoenes are reported.     

Total synthesis of an antitumor agent,mucocin, based on the "chiron approach"

The total synthesis of a powerful antitumor acetogenin, mucocin (1), was achieved through a palladium-catalyzed cross-coupling reaction of the THP-THF fragment 2 and a terminal butenolide 3. The key process for construction of the fragment 2 was chelation-controlled addition of ethynylmagnesium chloride to disilyl aldehyde 23a and condensation of the alkyllithium prepared therefrom with THP aldehyde 4 in the presence of CeCl(3). Synthesis of the lactone 3 relied on a novel approach by taking advantage of a radical cyclization of acyclic selenocarbonate 6. The three building blocks 4, 5a, and 6 were prepared stereoselectivly from D-galactose (7), 2,5-anhydro-D-mannitol (8), and L-rhamnose (9), respectively. A new and efficient method for desymmetrization of the C(2)-symmetrical compound 8 is also described.     

First total synthesis of aspinolide B, a new pentaketide produced by Aspergillus ochraceus

The first asymmetric total synthesis of Aspinolide B (1), a new 10-membered lactone discovered by chemical screening methods in the cultures of Aspergillus ochraceus, has been accomplished. The key steps included a selective Felkin-type addition of TMS-acetylene to aldehyde 3a and a Nozaki-Hiyama-Kishi coupling reaction to build the required 10-membered ring. This synthesis confirmed the absolute stereochemistry of aspinolide B, established through Helmchen's method and corrected its previously reported specific optical rotation.     

Acetoxyl group directed cyclization promoted by SmI2: directing group determined stereocomplementarity

Complete reversal of diastereoselectivity was observed in the SmI(2)-promoted ketyl-olefin coupling cyclizations of the hydroxy ketone or aldehyde and its acetate. For example, the stereodivergent synthesis of the epimeric five-membered-ring alcohols 2 and 4 has been accomplished through the SmI(2)-induced ketyl-olefin coupling cyclizations of the delta-hydroxy ketone 1 and delta-acetoxy ketone 3.     

Synthesis of bis-α-amino acids through proline catalyzed asymmetric α-amination of higher homologs of Garner's aldehyde

A very convenient synthesis of bis-α-amino acids from the higher homologs of Garner's aldehyde is reported. The key step is proline catalyzed asymmetric amination of the aldehydes using dibenzylazodicarboxylate. The aldehydes used are either commercially available or can easily be prepared from aspartic or glutamic acid. One of the two chiral centers in the bis-amino acids comes from the aldehyde and the other one is generated through the proline catalyzed reaction, which were high yielding and proceeded with very high diastereoselectivity (93–99%). The reported route offers a general method for the synthesis of the title compounds with desired stereochemical outcome.     

Enantioselective syntheses of (+)-xylarenal A and ent-xylarenal A

[reaction: see text] The total synthesis of the sesquiterpenoid xylarenal A is reported. This first synthetic entry to an eremophilane terpenoid with an exocyclic vinyl aldehyde unit involves the use of the bicyclic enone (+)-3, which after a gamma-oxidation and alpha'-allylation leads to the formation of the ketone (+)-8. After its acylation, an oxidative cleavage of the allyl side chain followed by alpha-methylenation of the resulting aldehyde gives (+)-xylarenal A (1). The synthesis of (-)-xylarenal A from (-)-3 is also reported. Moreover, the first total synthesis of the trinoreremophilane (+)-1alpha-hydroxyisoondetianone (5) is described.     

Synthesis of the anti-Helicobacter pylori agent (+)-spirolaxine methyl ether and the unnatural (2"S)-diastereomer

The first enantioselective synthesis of the anti-Heliocbacter pylori agent (+)-spirolaxine methyl ether 2b has been carried out in a convergent fashion establishing that the absolute stereochemistry of the natural product is in fact (3R, 2"R, 5"R, 7"R) after initial synthesis of the unnatural (2"S)-diastereomer 2a. The key step in the synthesis of (+)-spirolaxine methyl ether 2b involved a heterocycle-activated Julia-Kocienski olefination between benzothiazole-based spiroacetal sulfone 4b and phthalide aldehyde 3a. (2"R, 5"S, 7"S)-Spiroacetal sulfone 4b was prepared via cyclisation of protected dihydroxyketone 6b, which in turn was derived from the coupling of the acetylide derived from (R)-acetylene 24b with aldehyde 3a. Phthalide aldehyde 3a was prepared via intramolecular acylation of bromocarbamate 15, which was available via titanium tetrafluoride-(+)-BINOL-mediated allylation of 3,5-dimethoxybenzaldehyde 13. Union of the sulfone 4b and aldehyde 3a fragments successfully completed the enantioselective synthesis of (+)-spirolaxine methyl ether 2b. The synthesis of the unnatural (3R, 2"S, 5"R, 7"R)-diastereomer of spirolaxine methyl ether 2a was also undertaken in a similar manner by union of phthalide aldehyde 3a with (2"S, 5"S, 7"S)-spiroacetal sulfone 4a derived from (S)-acetylene 24a.     

Antimony(III) chloride-catalysed Biginelli reaction: a versatile method for the synthesis of dihydropyrimidinones through a different reaction mechanism

Antimony(III) chloride (20 mol %) in refluxing acetonitrile efficiently catalyses the synthesis of dihydropyrimidinones (50-90% yields) by the Biginelli reaction of aromatic aldehydes, acetoacetate esters and urea. This reaction proceeds through 3-ureido-crotonates followed by cyclisation with an aromatic aldehyde to the dihydropyrimidinone.     

A synthetic route to highly substituted 1,2,3,4-tetrahydroisoquinolines via Yb(OTf)3 -catalyzed diastereoselective ring opening of bridged oxazolidines: asymmetric synthesis of 2-azapodophyllotoxin

We herein report a robust and efficient synthetic route to highly functionalized enantiopure 1,2,3,4-tetrahydroisoquinolines (THIQs) from Garner aldehyde. We utilized the inherent chirality of Garner aldehyde through 1,2- and 1,3-/1,4-asymmetric inductions iteratively to obtain 1,2,3,4-tetrasubstitued THIQs using rigid and isolable bridged oxazolidines without any external chiral sources. All possible stereoisomers of bridged oxazoliodines were efficiently synthesized from L- and D-Garner aldehydes and transformed into fully functionalized THIQs via diastereoselective ring opening with various nucleophiles in the presence of Yb(OTf)(3). This methodology furnished four out of eight possible diastereomers of 1,2,3,4-tetrasubstituted THIQs despite the electronic nature of substituents on the aryl rings. Finally, the enantioselective synthesis of 2-azapodophyllotoxin was achieved with an overall yield of 35.4% (eight steps) from D-Garner aldehyde using this synthetic route.     

First Total Synthesis of (±)-13-Hydroxyneocembrene

First total synthesis of (±)-13-hydroxyneocembrene ( 1 ), starting from 6-methyl-5-hepten-2-one ( 6 ) and geraniol ( 7 ), is described. The key steps are (i) the addition of sulfur-stabilized carbanion 12 to aldehyde 9 , (ii) the synthesis of 18 by using phase-transfer catalyzed coupling reaction, and (iii) low-valent titanium-induced intramolecular coupling of oxo aldehyde 3 to afford the target molecule after the final deprotection.     

Oxime decorated cavitands functionalized through solvent-assisted grinding

In order to assemble supramolecular capsules, there is a need for reliable and effective synthetic methods for decorating cavitand-based host structures with appropriate functional groups. The synthesis of four different cavitands of significantly different depth and interior volume functionalized with four aldoxime groups capable of forming homomeric or heteromeric capsules through hydrogen bonding is reported. The final step in each synthesis, the aldehyde to oxime transformation, has been achieved in excellent yields through 'solvent assisted grinding'.