Synthesis of Dimethoxyfuranonaftoquinones

Recently some furanonaphthoquinones were isolated from Tabebuia species^2,3,4. The structures la, lb2, and li4 were assigned to three of these compounds (those of la and lb being later confirmed by synthesis^3,5,6). However, for the three other isolated compounds the spectroscopic data did not permit a decision to be made between the 2,3,4 - - - 4 isomeric pairs of structure lc and Id, le and lf ³, and lg and lh ⁴. Compounds la, lb, and le (or If), were tested in the KB cell culture assay and shown to be more active cytotoxic agents than lapachol^2,3, the probable biogenetic precursor of all of them.     

Aminohaloborane in Organic Synthesis. V.1 An Aldol-Type Condensation of Acetonitrile and Phenylacetonitrile with Benzaldehydes Using Secondary Aminodichloroborane

3-Phenyl-3-sec-aminopropionitriles (1) are not found in literature. We describe here a simple synthesis of 1 from acetonitriles (2) and benzaldehydes (3) using sec-aminodichloroboranes (4)² and triethylamine (5).     

Stereoselective Synthesis of 3-C-Branched-Chain Sugars by Aldol Reaction of Furanos-3-Uloses with Acetone

Abstract

Aldol reaction of 1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-erythro-pentofuranos-3-ulose (1) with acetone in the presence of aqueous K₂CO₃ afforded 3-C-acetonyl-1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-ribofuranose(2). Similar reaction of 1,2:5, 6-di-o-isopropylidene- α-D-ribo-hexofuranos-3-ulose (3) afforded 3-C-acetonyl-1,2:5, 6-di-o-isopropylidene- α-D-allofuranose (4) and (1R, 3R, 7R, 8S, 10R)-perhydro-8-hydroxy-5,5,10-trimethyl-2,4,6,11,14-pentaoxatetracyclo[8,3,1,0^1,8,0^3,7] tetradecane. The stereochemistry of the new chiral centers were determined by ¹H NOE experiments.     

An Efficient Stereoselective Synthesis of a Tricyclic Intermediate for the Synthesis of Derivatives of Abietic and Podocarpic Acids

For many years the synthesis of diterpene acids has attracted the attention of organic chemists. Kröniger and Wheeler¹ reported that the condensation of the dimethylate 1a with methyl malonate gave the cis compound 2a which on heating with palladised charcoal was converted into the trans isomer 3a. Compound 3a is a promising intermediate in the synthesis of derivatives of both abietic and podocarpic acids, while 2a could be a starting material for the synthesis of cis fused diterpene acids. However, the route to 2a and 3a was inefficient; 1a was only available as the minor component of a mixture with its epimer 1b; and the yield for the stage 2a + 3a was poor.     

Asymmetric Synthesis of (S)-Homoproline and (S)-Homopipecolic Acid1

As for (S)—homoproline (3) there is a marked discrepancy between the directions of the optical rotation reported by two groups of chemists3,4. Here we wish to communicate novel asymmetric syntheses of (S)—homoproline (3) and (S)—homopipecolic acid (4) carried out in connection with our asymmetric cyclization studies². We also examined catalytic potentialities of these unnatural β-amino acids in asymmetric aldol cyclization.     

A New Synthesis of 3-Deoxy-D-arabino-hexose and its Tautomeric Equilibrium

Abstract

The title compound was synthesized in four steps from D-glucono-1,5-lactone. Reduction of 2,4,6-tri-O-benzoyl-3-deoxy-D-arabino-hexono-1,5-lactone (1) with disiamylborane afforded 2,5,6-tri-O-benzoyl-3-deoxy-D-arabino-hexopyranoae (2) which, on debenzoylation, gave 3-deoxy-D-arabino-hexoae (3). Tautomeric equilibrium of 3 was studied by ¹H and ¹³C NMR spectroscopy.     

Synthesis of Bioactive Pyrethroid, 3-Phenoxybenzyl 1R-trans-2, 2-Dimethyl-3-(2-chloro-1-propenyl) Cyclopropanecarboxylate

The title compound 1 has been prepared from (+)-3-carene (2) and found to have the same order of activity as its IR-cis isomer 3 reported by us earlier¹ The key intermediate methyl IR-trans-2, 2-dimethyl-3-(2-oxopropyl)cyclopropanecarboxylate (4) has been characterised.     

1-Thioglycopyranosyl Esters of N-Acylamino Acids

Abstract

Fully protected 1-thioglycopyranosyl esters of N-acylamino acids (5, 6, and 7) were prepared by condensation of methyl 2, 3, 4-tri-O-acetyl-1-thio-β-d–glucopyranuronate (1), 2, 3, 4-tri-O-acetyl-1-thio-l–arabinopyranose (2), and 2, 3, 4-tri-O-acetyl-1-thio-D-arabinopyranose (3) with pentachlorophenyl esters of N-acylamino acids in the presence of imidazole. The ¹³C NMR chemical shifts of the starting 1-thio sugars and the 1-thiol ester products are reported.     

Synthesis of Coleon U

The recent publication by Matsumoto¹ of a synthesis of Coleon U²(1) prompts us to present our own preparation of this poly-hydroxy diterpene as the tri-O-methyl (12a) and tetra-O-methyl ethers (12b). In a previous communication³ we outlined our approach which is aimed at several similar natural products such as Coleon C⁴ (1b), Lycoxanthol⁵ (2), etc. and differs considerably from that of the Japanese group. Formally at least, the two syntheses start with the same material, (+) ferruginol methyl ether 5a. In our case the latter was prepared by recorded methods from methyl O-methyl podocarpate after introducing the iso-propyl sidechain⁶ (→4), transforming the C.4 methoxycarbonyl residue to a methyl⁷ (→5a, ferruginol methyl ether) which was oxidised at the benzylic position of the B ring to give sugiol methyl ether 5b.     

A Facile Synthesis of 2-Hydroxy-6-Methylacetophenone

Recently, we identified 2-hydroxy-6-methylacetophenone (3) and 2-acetoxy-6-methylacetophenone (4) as exocrine compounds in several neotropical species of ants in the dolichoderine genus Hypoclinea. Although 3 has been reported at least four times in the literature as a synthetic intermediate or as the object of a nuclear magnetic resonance study, neither 3 nor 4 had been reported as natural products, and 4 is a novel compound.^2,3,4,5     

Synthesis of Methyl 1-Thio-L-Rhamnopyranoside-Derivatives

Abstract

Both anomers of methyl 1-thio-L-rhamnopyranosides were prepared through methylation of the corresponding isothiouronium salt. 2,3-0-Isopropylidene-, benzylidene-and the until now unknown diphenyl-methylene acetals were synthesized. Phase-transfer catalysed benzylation and LiA1H₄-AlCl₃-type hydrogenolysis of benzylidene acetals were used to obtain partially benzylated derivatives. Comparing the C NMR data of the synthesized compounds with those of their 0-glycoside analogues revealed that the 0→S exchanges at the anomeric centres caused drastic upfield shifts (～15 ppm) at C-1 and moderate downfield shifts at C-2 and C-5, as well. The chemical shift values of other carbons are not sensitive to the 0→S replacement.     

A Conventient Synthesis of 3-Hydroxy-4-chromanone Using Iodobenzene Diacetate

A useful synthesis of 3-hydroxy-4-chromanone (6) is not currently available. Lead tetraacetate oxidation of 4-chromanone (4) yields the C(3) acetoxy derivative but this compound could not be deacetylated to 6.¹ Recently Donnelly and Maloney reported² that the Algar-Flynn-Oyamada reaction (H₂O₂/CH₃OH/NaOH), which is commonly used for the conversion of o-hydroxychalcones (1) into 3-hydroxyflavanone (2) and 3-hydroxyflavones (3), does not yield 6 when applied to o-hydroxya-crylophenone 1 (R = H). The authors found that under less basic conditions using K₂CO₃ some 6 is formed but the major product is catechol. These observations clearly indicate the necessity of developing a method for making 6. The present note describes a staightforward way of preparing 3-hydroxy-4-chromanone (6) in good yield.     

Synthesis of 1-Thio-N-acetylmuramoyl-L-alanyl-D-isoglutamine Derivatives,and Their Biological Activities. XX

Abstract

In the course of an investigation² on the relationship between the immunoadjuvant activity and the structure of the carbohydrate moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP), which is the minimal, immunoadjuvant-active component of bacterial cell-wall peptidoglycan, we demonstrated that not only is restricted configuration of the sugar moiety important for the activity² but also that chemical modifications^3–5 of the functional groups in the carbohydrate moiety produce various, important effects on the manifestation of activity. It has been shown that lipophilic derivatives^6–8 of MDP bearing the lipid moiety at C-6 of the sugar skeleton, or at the end of the peptide chain, have strong antitumor and anti-infection activities that are not for MDP itself. In addition, we have also observed that introduction^3b,9,10 of lipophilic character at C-2 in muramoyl-L-alanyl-D-isoglutamine, or at C-6 in N-acetyl-6-amino-6-deoxy-muramoyl-L-alanyl-D-isoglutamine, causes potent antitumor activity based on the immune reaction, as well as strong, immunoadjuvant activities.     

Synthesis of 2, 3-dideoxy-4-O-p-methoxybenzyl-L-erythro-hex-2-enono-1, 5-lactone

The synthesis of 2, 3-dideoxy-4-O-p-methoxy-benzyl-L-erythro-hex-2-enono-1, 5-lactone 9 from L-serine, using (1RS, 3S)-3, 4-isopropylidene-1-methoxy-1-phenylthio-butan-2-one 2 as key chiral intermediate, is described. Compound 9 is an interesting chiral precursor for the synthesis of L-sugars.     

Synthesis of 2-Carbamoyl-2-Deoxy Glycosides

Abstract

Recently we have reported the addition of trichloracetyl isocuyanate to glycals 1 _1,2,3. The reaction led to the highly stereoselective formation of a mixture of unstable [2+2] and [4+2] cycloadducts 2 and 3. The isocyanate adds to the glycal moiety anti to the substituent at C-3. The addition of benzylamine to the reac6tion mixture led to N-deprotection of 2 and allowed us to isolate stable bicyclic β-lactams 4 _1-3. We have shown also that 2 (a mixture of α-L-gluco and β-L-manno isomers) obtained from L-rhamnal 1 (R¹[dbnd]Ac, R²[dbnd]CH₃ under high pressure, when treated with methanol, underwent a rapid trans opening of the four-membered ring to give respective glycosides 5(β-L-gluco and α-L-manno isomers). On the other hand 3 (R¹[dbnd]Ac, R²[dbnd]CH₃) under the same conditions added a molecule of methanol to the C[dbnd]N double bond affording 6.     

Stereoselective Total Synthesis of Sesquiterpenoids: (+)-Sativene and (+)-Cyclosativene

Abstract

The well-known tricyclic sesquiterpenoid (?)-sativene, isolated in 1965 from Helminthosporium sativum and shown to possess structure and absolute configuration as indicated by structure 1 ³, has been implicated^3,4 as an intermediate in the biogenesis of the fungal toxin (?)-helminthosporal (2)⁵. Two total syntheses of the racemic modification of sativene have been reported^6,7. A closely related sesquiterpenoid, (+)-cyclosativene, was isolated from Abies magnifica A. Murr. and was shown to possess structure 3 ^8,9. The absolute configuration of this material, although not established unambiguously, has been proposed¹⁰ as indicated by formula 3. The total synthesis of cyclosativene has not as yet been achieved directly, although it has been obtained indirectly via acid-promoted rearrangement of sativene^8,9,11,12. We report herein a total synthesis of (+)-sativene (4) and (+)-cyclosativene (3) via a stereoselective route which unambiguously establishes the absolute configuration of both natural products.     

Carbon Atom Insertion: A One-Step Synthesis of Tricyclo[3.2.1.02,7]octanes and Tricyclo[4.1.0.02,7]heptanes from Cyclohexenes1

Reinarz and Fonken have reported² that the dibromocarbene adduct (1) of 1-methylcyclohexene, upon reaction with methylllthium at 0° in ether, produced exclusively the bicyclobutanes 2 and 3 in relative yields of 60% and 40%, respectively. We have prepared 1 by the phase-transfer method³ of Makosza and Fedorynski in a yield of 67%, found these previous results to be completely reproducible in our hands, and determined the combined yield of the two products (2 and 3) to be 67% also. Thus, the overall     

Synthesis of N-[2-S -(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-Thio-D-Lactoyl]-L-alanyl-D-isoglutamine

Abstract

N-[2-S-(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-thio-D-lactoyl]-L-alanyl-D-isoglutamine, in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1).

Treatment with sodium acetate of the 3-O-mesylate, derived from 1 by 4,6-O-isopropylidenation and subsequent mesylation, gave allyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-allopyranoside (4). When treated with potassium thioacetate, the 3-O-mesylate, derived from 4, afforded allyl 2-acetamido-3-S-acetyl-2-deoxy-4,6-0-isopropylidence-β-D-glucopyranoside (6). S-Deacetylation of 6, condensation with 2-L-chloropropanoic acid, and subsequent esterification, gave the 3-s[D-1(methoxycarbonyl)ethyl]-3-thio-glucopyranoside derivative (7). Coupling of the acid, derived from 7, with the methyl ester of L-alanyl-D-isoglutamine, and subsequent hydrolysis, yielded the title compound.     

The Synthesis of Hydronaphthalenes from m-Toluic Acid via Cyclization of Thioacetal Monosulfoxides

We recently developed a convenient route to hexahydronaphthalenols such as 5 (R=CO₂CH₃ or CH₃) starting from m-toluic acid (1)¹. The key features of the route involved reduction-alkylation of the toluic acid to the dihydro derivative 2 ², subsequent deprotection and oxidation of the side chain primary alcohol, and acid-catalyzed cyclization of the resulting aldehyde 4. In the case of the dimethylnaphthalenols 5 (R=CH₃), conversion of the angular carboxylic function to the methyl group was effected prior to cyclization via reduction of the p-toluenesulfonic ester of the neopentyl alcohol 3 (R=CH₂OH) using lithium triethylborohydride³.     

Phospha-alkynes - Useful Building Blocks in Organic Chemistry1

Abstract

The syntheses of phospholes (7, [3+2]-cycloaddition), bicyclophosphaalkenes (17, [4+2]-cycloaddition), and phosphabenzenes (15, [4+2]-cycloaddition followed by an extrusion process) starting from the phosphaalkynes (4) are described. The 2–Dewar phosphabenzene 18, obtained from the cyclobutadiene 21 and 4 (R =^tBu), is the starting material for the synthesis of the valency isomers 19, 20, 22, and 23.