Synthesis of 1-acetyl-2-silyoxycycloheptane derivatives via highly stereoselective formal [5+2] cycloaddition reaction

A stereoselective [5+2] cycloaddition reaction using a new five-carbon unit, that has a dicobalt acetylene complex moiety and an enol silyl ether moiety, was developed. In the presence of a Lewis acid, the five-carbon unit reacted with an enol triisopropylsilyl ether to give a 1-acetyl-2-silyoxycycloheptane derivative, in which the three contiguous substituents on the seven-membered ring arrange cis to each other.     

Fluorescent sensing of triphosphate nucleotides via anthracene derivatives

A nucleotide is composed of a nucleobase, a five-carbon sugar, and phosphate groups. Recognition of these three sites can provide useful information for the development of selective fluorescent receptors for a specific nucleotide. In this paper, anthracene derivatives with two imidazolium groups at the 1,8- and 9,10-positions, quaternary ammonium groups, or the boronic acid group were examined for the recognition of nucleotides, such as ATP, GTP, CTP, TTP, UTP, ADP, and AMP, via fluorescence changes. The anthracene group provides the interaction between the bases of the nucleotides. The imidazolium and quaternary ammonium groups induce hydrogen bonding interactions with the phosphate groups of the nucleotides. The boronic acid group can interact with the ribose of the nucleotides.     

Total synthesis of 5-desoxyleukotriene D. A new and useful equivalent of the 4-formyl-trans, trans-1,3-butadienyl anion

The first total synthesis of 5-desoxyleukotriene D ($\text{14}$) is reported. The route of synthesis utilizes a novel method for five-carbon chain extension. The availability of $\text{14}$ allowed experimental demonstration that the 5-hydroxyl function is important for biological activity of the slow reacting substances.     

Proline-mediated enantioselective construction of tetrahydropyrans via a domino aldol/acetalization reaction

Highly enantioselective synthesis of tetrahydropyrans was accomplished via a domino proline-mediated aldol reaction/intramolecular acetal formation from an aldehyde and inexpensive aqueous tetrahydro-2H-pyran-2,6-diol as a five-carbon unit.     

Synthesis of the glycosphingolipid beta-galactosyl ceramide and analogues via olefin cross metathesis

The preparation of the glycosphingolipid galactosyl ceramide from an orthogonally protected five-carbon building block is described. The main chain of the lipid is installed via a highly stereoselective olefin cross metathesis reaction. The methodology permits the facile preparation of glycolipids which vary in the length of the main carbon chain.     

Synthesis of an electronically-tuned minimally interfering alkynyl photo-affinity label to measure small molecule–protein interactions

We report the synthesis of an electronically-tuned minimally interfering photo-affinity label (MI-PAL), a compact five-carbon tag functionalized with an alkyl diazirine and alkyne handle. MI-PAL is compatible with protein photo-conjugation, click chemistry and mass spectrometry and readily installed to complex molecules for biological target identification.     

A general protocol for the regio high yielding opening of different glycidol derivatives

Differently protected glycidol derivatives (with Bn, TBDPS, TBS and MPM groups) have been tested for regioselective ring opening with vinylmagnesium bromide in order to obtain useful five-carbon functionalised homoallylic alcohols. Careful choice of the reagents and experimental conditions allowed a general access to important chiral synthons for asymmetric synthesis.     

Total synthesis and structural confirmation of (+)-longicin

A stereocontrolled total synthesis of (+)-longicin, a representative of the class of mono-THF-acetogenins, is described. The strategy involves the utilization of d- and l-glutamic acids as chirons that correspond to two five-carbon segments harboring stereogenic centers at C4 and at C17 of the C(32) polyketide-derived natural product. The use of Grubbs' RCM reaction as a novel "chain elongation" strategy for the synthesis of acetogenin-type structures and a new protocol for butenolide incorporation are also described. [structure: see text]     

Divergent synthetic routes for ring expansion or cyclization from 1,4-allylic diol derivatives via gold(I) catalysis or zinc(II) mediation

A new efficient method was developed to transform cyclic alkanols into one-carbon higher homologated ketones using various esters as the leaving groups through gold-catalyzed allylic cation-promoted pinacol-type rearrangement. This reaction, coupled with oxy-Cope rearrangement, provided a new strategy to synthesize five-carbon homologated ring ketones. In addition, using ZnBr(2), 2,5-dihydrofuran products were obtained in moderate to good yields via an intramolecular cyclization process.     

Co-complexes derived from alkene insertion to alkyne-dicobaltpentacarbonyl complexes: insight into the regioselectivity of pauson-khand reactions of cyclopropenes

Described are the X-ray crystallographic and spectral properties of Co-complexes that were isolated from two Pauson-Khand reactions of chiral cyclopropenes. These are the first examples of isolated Co-complexes derived from the putative alkene-insertion intermediates of Pauson-Khand reactions. The binuclear Co-complexes are coordinated to mu-bonded, five-carbon "flyover" carbene ligands. It is proposed that the complexes result from cyclopropane fragmentation subsequent to alkene insertion. The observation of these metal complexes provides a rationale for the origin of regioselectivity in Pauson-Khand reactions of cyclopropenes.     

Stereoselective synthesis of cycloheptanone derivatives via an intermolecular [5 + 2] cycloaddition reaction

[reaction: see text] A [5 + 2] cycloaddition reaction of a new five-carbon unit was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl(2), [5-benzoyloxy-2-(triisopropylsiloxy)-1-penten-3-yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield seven-membered dicobalt acetylene complexes in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity. The cycloadducts can be easily converted into various kinds of cycloheptanone derivatives.     

A new and practical five-carbon component for metal-catalyzed

Described herein is an efficient preparative scale synthesis of 1-(2-methyoxyethoxy)-1-vinylcyclopropane and the investigation of the utility of this reagent as a new five-carbon component in metal-catalyzed [5 + 2] cycloadditions. A new cycloaddition procedure is also described that proceeds up to 12-fold faster and with 10-fold less catalyst than previously described, providing cycloheptenones in many cases in minutes and in isolated yields of 75-97%. The procedure is readily conducted on a small or large scale (up to 100 mmol thus far).     

Synthesis and HPLC evaluation of carboxylic acid phases on a hydride surface

Three organic moieties containing carboxylic acid functional groups are attached to a particulate silica surface through silanization/hydrosilation. Two compounds (undecylenic acid and 10-undecynoic acid) have 11 carbon chains and the other is a five-carbon acid (pentenoic acid). Bonding is confirmed through carbon elemental analysis, diffuse reflectance infrared fourier transform spectroscopy, and carbon-13 and silicon-29 CP-MAS NMR spectroscopy. The bonded phases are tested by HPLC using PTH amino acids, nucleic acids, theophylline-related compounds, anilines, benzoic acid compounds, choline, and tobramycin. The latter two compounds are used to investigate the aqueous normal phase properties of the three bonded materials.     

Reductive fragmentation of carbohydrate anomeric alkoxy radicals. Synthesis of alditols with potential utility as chiral synthons

A series of anomeric nitrate esters and N-phthalimido glycosides of carbohydrates in furanose and pyranose forms have been synthesized in order to generate the corresponding alkoxy radicals and study the C1-C2 fragmentation reaction under reductive conditions. This reaction constitutes a two-step method for the transformation of carbohydrates into the corresponding alditols with one less carbon. Using this methodology, interesting four- and five-carbon building blocks for natural products synthesis possessing D-erythritol, D-threitol, D-xylitol, and D-arabinitol stereochemistry have been prepared. The synthesis of 1,2-O-isopropylidene-beta-L-threose (40) and 1-acetamido-2,4,5-tri-O-acetyl-D-arabinitol (50) have also been achieved from 1,2:5,6-di-O-isopropylidene-beta-D-glucofuranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranose, respectively.     

Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of trans-vinylcyclopropane-enes

Vinylcyclopropane (VCP) has been well applied as a five-carbon component, rather than a three-carbon component, in transition-metal catalyzed cycloadditions. Here we demonstrate a Rh(I)-catalyzed [3 + 2] reaction of trans-VCP-enes, where VCP acts as a three-carbon synthon to furnish five-membered carbocycles. This novel cycloaddition is efficient in generating bicyclic cyclopentanes in good yields from simple and easily prepared substrates. When cis-VCP-ene is used as the substrate, VCP acts as a five-carbon unit to give a [5 + 2] cycloadduct. Rationalization of the [3 + 2] and [5 + 2] cycloadditions of VCP-enes has been proposed.     

Synthesis of 2-methyl-D-erythritol via epoxy ester-orthoester rearrangement

The biomimetic epoxy ester[bond]orthoester rearrangement has been applied to a new synthesis of 2-methyl-D-erythritol, a branched five-carbon sugar of importance to the deoxyxylulose pathway of isoprenoid biosynthesis. The intermediate orthoacetate is one of the few [2.2.1]-orthoesters to have been reported. Labeling studies with O-18 indicated that this reaction proceeds exclusively via a 5-exo cyclization. NMR analysis of chiral esters indicated an ee of 87% for the starting epoxide and an ee of 86% for the product. This route represents a rapid and convenient method for the synthesis of 2-methyl-D-erythritol and is expected to be useful for generating isotopically labeled intermediates for biochemical studies.     

Discovery of a Dual Function Cytochrome P450 that Catalyzes Enyne Formation in Cyclohexanoid Terpenoid Biosynthesis

The 1,3-enyne moiety is commonly found in cyclohexanoid natural products produced by endophytic and plant pathogenic fungi. Asperpentyn ( 1 ) is a 1,3-enyne-containing cyclohexanoid terpenoid isolated from Aspergillus and Pestalotiopsis. The genetic basis and biochemical mechanism of 1,3-enyne biosynthesis in 1 , and other natural products containing this motif, has remained enigmatic despite their potential ecological roles. Identified here is the biosynthetic gene cluster and characterization of two crucial enzymes in the biosynthesis of 1 . A P450 monooxygenase that has a dual function, to first catalyze dehydrogenation of the prenyl chain to generate a cis-diene intermediate and then serve as an acetylenase to yield an alkyne moiety, and thus the 1,3-enyne, was discovered. A UbiA prenyltransferase was also characterized and it is unusual in that it favors transferring a five-carbon prenyl chain, rather than a polyprenyl chain, to a p-hydroxybenzoic acid acceptor.     

Ring-expansion of thioacetal ring via bicyclosulfonium ylide. Effect Of protic nucleophile on ylide intermediate

The reaction of 2-(3-diazo-2-oxopropane-1-yl)-2-methyldithiolane 9a, 2-(4-diazo-3-oxobutane-2-yl)-2-methyldithiolane 9c, and 2-(3-diazo-2-oxopropane-1-yl)-2-methyl-1,3-dithiane 9b with Rh(2)(OAc)(4) gave three-carbon ring-expansion products dithiocan-2-en-1-ones 13a, 13c and dithionan-2-en-1-one 13b, respectively. 2-(5-Diazo-4-oxopentyl)-2-methyldithiolane 9e also gave the five-carbon ring-expansion products dithionan-3-en-1-one 13e and 5-methylenedithionane-1-one 13'e. On the other hand, reaction of 2-(4-diazo-3-oxobutyl)-2-methyldithiolane 9d in the presence of AcOH gave the four-carbon ring-expansion product 16d substituted by an acetoxyl group. In addition, the reaction of 2-(3-diazo-2-oxopropyl)-2-methyl-3-oxathiolane 9f in the absence of AcOH gave 4-oxa-7-thiocan-2-en-1-one 19 via a sulfonium ylide intermediate, whereas, in the presence of AcOH, an alternative regioisomer 20 was also formed competitively with 19 via an oxonium ylide intermediate.     

Production of Xylitol from D-Xylose byDebaryomyces hansenii

Xylitol, a naturally occurring five-carbon sugar alcohol, can be produced from D-xylose through microbial hydrogenation. Xylitol has found increasing use in the food industries, especially in confectionary. It is the only so-called “second-generation polyol sweeteners” that is allowed to have the specific health claims in some world markets. In this study, the effect of cell density on the xylitol production by the yeastDebaryomyces hansenii NRRL Υ-7426 from D-xylose under microaerobic conditions was examined. The rate of xylitol production increased with increasing yeast cell density to 3 g/L. Beyond this amount there was no increase in the xylitol production with increasing cell density. The optimal pH range for xylitol production was between 4.5 and 5.5. The optimal temperature was between 28 and 37°C, and the optimal shaking speed was 300 rpm. The rate of xylitol production increased linearly with increasing initial xylose concentration. A high concentration of xylose (279 g/L) was converted rapidly and efficiently to produce xylitol with a product concentration of 221 g/L was reached after 48 h of incubation under optimum conditions.

     

Biosynthesis of phycobilins. Formation of the chromophore of phytochrome, phycocyanin and phycoerythrin

Phycobiliproteins play important roles in photomorphogenesis and photosynthesis. The light-absorbing chromophores of the phycobiliproteins are linear tetrapyrroles (bilins) very similar in structure to the mammalian bile pigments. 5-Aminolaevulinate (5-ALA) is the first committed intermediate in phycobilin synthesis. The biosynthesis of 5-ALA, destined for phycobilins, occurs via the five-carbon pathway, now well established for tetrapyrrole synthesis in plants and distinct from the mammalian pathway. The phycobilins are formed by reduction of biliverdin which results from the synthesis and degradation of haem. This haem is an essential intermediate in the biosynthesis of phycobilins. Phycocyanobilin, the blue-green pigment found in certain algae and cyanobacteria, is formed from biliverdin via phytochromobilin, the chromophore of phytochrome. This leads to the likelihood that phytochromobilin is formed as an end product, or intermediate, in the synthesis of all phycobilins.