Functionalisation of saturated hydrocarbons. Part 9. Oxidation of patchouli alcohol by the ‘gif system’: Isolation and organoleptic properties of three new ketonic derivatives

Oxidation of patchouli alcohol ( 1 ) using the ‘Gif system’ afforded as major isolated products three new ketonic derivatives 16–18 . The structures of these compounds were established by spectral techniques including 2D-NMR. Ketones 16–18 display interesting organoleptic properties.     

Syntheses of methyl α-dl-mycaminoside, methyl α-dl-oleandroside, methyl β-dl-cymaroside, methyl α-dl-tyveloside and methyl α-dl-chromoside C

Five rare hexoses, which are components of antibiotics or cardiac glycosides, have been synthesized as methyl glycosides through a common intermediate methyl 2,3-dehydro-2,3,6-trideoxy-α-dl glucopyranoside (7). Epoxidation and subsequent treatment with dimethylamine of7 afforded methyl α-dl-mycaminoside (9). The addition reaction of MeOH to12 gave methyl α-dl-oleandroside (15) and methyl β-dl-cymaroside (17). The hydroxymercuration and subsequent reduction of12 afforded methyl α-dl-chromoside C (19) and methyl β-dl-tyveloside (25).     

Nucleic-Acid Analogues with Constraint Conformational Flexibility in the Sugar-Phosphate Backbone (‘Bicyclo-DNA’). Part 1. Preparation of (3S,5′R)-2′-Deoxy-3′,5′-ethano-αβ-D-ribonucleosides (‘Bicyclonucleosides’)

We describe the synthesis of 2′-deoxy-3′,5′-ethano-D -ribonucleosides 1 – 8 (= (5′,8′-dihydroxy-2′-oxabicyclo-[3.3.0]oct-3′-yl)purines or -pyrimidines) of the nucleobases adenine, thymine, cytosine, and guanine. They differ from natural 2′-deoxyribonucleosides only by an additional ethylene bridge between the centers C(3′) and C(5′). The configuration at these centers (3S,5′R) was chosen as to match the geometry of a repeating nucleoside unit in duplex DNA as close as possible. These nucleosides were designed to confer, as constituents of an oligonucleotide chain, a higher degree of preorganization of a single strand for duplex formation with respect to natural DNA, thus leading to an entropic advantage for the pairing process. The synthesis of these ‘bicyclonucleosides’ was achieved by construction of an enantiomerically pure carbohydrate precursor 18 / 19 (Schemes 1), which was then converted to the corresponding nucleosides by known methods in nucleoside synthesis (Schemes 2 and 3). In all cases, both anomeric forms of the nucleosides were obtained in pure crystalline form, the relative configuration of which was established by ¹H-NMR-NOE spectroscopy. A conformational analysis of the nucleosides with β-configuration at the anomeric center by means of X-ray and ¹H-NMR (including NOE) spectroscopy show the furanose part of the molecules to adopt uniformly a 1′exo-conformation with the base substituents preferentially in the anti-range in the pyrimidine nucleosides (anti/syn ca. 2:1) distribution in the purine nucleosides (in solution).     

Radical copolymerization of acrylic monomers. VIII. Copolymerization of methyl methacrylate with methyl α-p-chlorobenzylacrylate and methyl methacrylate with methyl α-p-methoxybenzylacrylate

Free-radical copolymerization of methyl methacrylate with methyl α-p-chlorobenzylacrylate and methyl methacrylate with methyl α-p-methoxybenzylacrylate have been studied in benzene solution at 40°C. Although a simple copolymerization model fits the composition data, the kinetic behavior of both copolymerization systems are analyzed from simple and reversible copolymerization models, taking into account the relatively low ceiling temperature of both methyl α-(p-substituted benzyl)acrylates and considering that the overall rate of copolymerization drastically decreases with the increase of the corresponding methyl α-(p-substituted benzyl)acrylate molar fraction in the feed.     

Photochemical Reactions. Part 67. photochemistry of saturated aliphatic and cyclic β-keto sulfoxides (Cα?S)- and α-cleavage – A new case of photostereomutation

The photochemical behaviour of saturated aliphatic ( 2, 4 , and 5 ) and bicyclic ( 18 and 19 ) β-keto sulfoxides has been studied. Photostereomutation of the sulfoxide group was observed on irradiation of 4a, 4b, 18 , and 19 . Most likely an internal energy transfer from the excited carbonyl to the sulfoxide group is operating on direct irradiation of such compounds. Prolonged photolysis of an aliphatic β-keto sulfoxide, which is nonalkylated a t the α-carbon ( 2 ), yielded a product due to preferential (C_α-S)-cleavage ( 24 ). Mono- ( 4 ) and dialkylated- ( 5 , 6 , and 8 )analogues primarily afforded products due to α-cleavage ( 26–31 and 32 ). The carboxylic acid S-methylesters ( 26–31 ) were exclusively formed by an intermolecular path. Prolonged irradiation of the bicyclic β-keto sulfoxides 18 and 19 favored the formation of a desulfurized compound 34 due to initial ( C_α-S )-cleavage.     

‘Mixed’ β-peptides: A unique helical secondary structure in solution. Preliminary communication

β-Hexapeptides 1–5 and a β-dodecapeptide 6 with sequences containing two different types of β-amino acids (aliphatic proteinageous side chains in the 2- or in the 3-position) have been prepared. CD (Fig. 1) and NMR measurements indicate that, with one exception, the secondary structures formed by these new β-peptides differ from those of isomers studied previously. Detailed NMR analysis of the β-hexapeptide 5 (with alternating β²,β³-building blocks) and molecular-dynamics simulations have produced a minimum energy conformation (Fig. 2,b)which might be described as a novel irregular helix containing ten- and twelve-membered H-bonded rings. This demonstrates the great structural variability of β-peptides, since three different helical secondary structures have been discovered to date.     

Synthetic applications of electrochemically produced α-methoxyamides. Part 2. Oxidation of hydroxyproline derivatives

The electrochemical methoxylation of N-acetyl-4-hydroxyproline esters has been investigated. Both the free alcohol 3 and the corresponding 4-acetoxy derivative 4 as well as the cis-4-acetoxyproline 17 are methoxylated anodically preferentially at C(5), giving a mixture of stereoisomeric methoxy compounds. These mixtures can be used for further substitution as exemplified by the allylation of the methoxylated 4-acetoxy derivatives, giving substitution products preferentially trans to the acetoxy group although with low selectivity. The low selectivity is discussed in terms of kinetic vs. thermodynamic control.     

Photochemical Rearrangement of a Steroidal α,β-Epoxylactone. Photochemical reactions,XI [1]

The UV. irradiation of 17β-acetoxy-4α, 5α-epoxy-2-oxaandrostan-3-one ( 7 ) yields 17β-acetoxy-2-oxa-10(5 → 4)abeo-4ζ (H)-androsta-3,5-dione ( 11 ). A non-photochemical synthesis of 11 , proceeding in lower yield, is also described.     

Radical polymerization and copolymerization of methyl α-(2-carbomethoxyethyl)acrylate,a dimer of methyl acrylate,as a polymerizable α-substituted acrylate

Polymerization and copolymerization of methyl α-(2-carbomethoxyethyl)acrylate (MMEA), which is known as a dimer of methyl acrylate, were studied in relation to steric hindrance-assisted polymerization. The propagating polymer radical from MMEA was detected as a five-line spectrum and quantified by ESR spectroscopy during the bulk polymerization at 40–80°C. The absolute rate constants of propagation and termination (κ_p and κ_t) for MMEA at 60°C (κ_p = 19 L/mol s and κ_t = 5.1 × 10⁵ L/mol s) were evaluated using the concentration of the propagating radical at the steady state. The balance of the propagation and termination rates allows polymer formation from MMEA. The polymerization rate of MMEA at 60°C was less than that of MMA by a factor of about 4 at a constant monomer concentration. Although no influence of ceiling temperature was observed at a temperature ranging from 40 to 70°C, addition-fragmentation in competition with propagation reduced the molecular weight of the polymer. The content of the unsaturated end group was estimated to be 0.1% at 60°C to the total amount of the monomer units consisting of the main chain. MMEA exhibited reactivities almost similar to those of MMA toward polymer radicals. It is concluded that MMEA is one of the polymerizable acrylates bearing a substituted alkyl group as an α-substituent. Characterization of poly(MMEA) was also carried out. © 1996 John Wiley & Sons, Inc.     

Enantioselective separations by capillary GC on derivatized cyclodextrins. Part 1: Separation of some racemic 2,2-dialkyl-4-alkoxycarbonyl-1,3-dioxolane derivatives on permethylated α-, β- and γ-cyclodextrins

The enantioseparation of some 2,2-dialkyl-4-alkoxycarbonyl-1,3-dioxolane derivatives, which are important intermediates in the total synthesis of a number of biologically active compounds, was studied by means of capillary gas chromatography (CGC). The chromatographic results, obtained on columns coated with permethylated α-, β- and γ-cyclodextrin respectively, are reported. Out of sixteen compounds, thirteen could be separated with a resolution superior to 1,2. One racemate could not be separated on any of the columns. Considerations concerning the separation mechanism are proposed.     

Pterin Chemistry. Part 92.. Loading experiments with 6α,β-tetrahydro-L-[3′-2H1] biopterin

6α,β-Tetrahydro-L -[3′-²H₁]biopterin ([3′-²H₁]- 1 ) was administered orally to two primapterinuric patients in order to investigate the biosynthetic pathway of 7-substituted pterins in humans. L -Primapterin ( 2 ) and L -biopterin were isolated from urine after loading and measured by GC/MS. L -Biopterin and L -primapterin were labelled with ²H to an equal extent. From this result, one can conclude that L -primapterin is formed from tetrahydro-L -biopterin, very probably via an intramolecular rearrangement.     

Poly(alkylene oxide) ionomers. XI. Polymerization and copolymerization of methyl ω-epoxyundecanoate and characterization of the polymers

Methyl 10-undecenoate was epoxidized in nearly quantitative yield with m-chloroperoxy-benzoic acid to methyl 10,11-epoxyundecanoate. The functional epoxide monomer was polymerized by the reaction product of triethylaluminum/water/acetylacetone (1.0/0.5/1.0) to a high molecular weight elastomer having pendent carboxyl groups, and a molecular weight distribution near the most probable distribution. With the same initiator system, methyl 10,11-epoxyundecanoate was copolymerized with ethylene oxide, propylene oxide, 1-butene oxide, 1-hexene oxide, phenyl glycidyl ether, epichlorohydrin, and 4,4,4-trichloro-1-butene oxide. The copolymers were typically high in molecular weight, elastomeric, and had methyl 10,11-epoxyundecanoate incorporations similar to the initial feed ratio of comonomers. The new family of functional polymers were characterized by their infrared and NMR spectra, dilute solution viscosity and thermal transitions.     

Solvolysis of α-Bromo-p-aminostyrene. Mesomeric vinyl cations,Part IV

The preparation of α-bromo-p-aminostyrene ( 1b ) and its solvolysis rates and products have been reexamined in detail. In buffered 50 vol % aqueous dioxane between p_H* 13 and 3 the reaction rate is independent of hydrogen ion concentration. The ratio of the solvolysis products, viz. p-aminoacetophenone ( 3b ) and p-aminophenylacetylene ( 5a ), however, varies with the p_H* and with the buffer concentration. These findings confirm the unimolecular (S_N1-E1) mechanism involving an intermediate vinyl cation. The acid-catalysed hydration mechanism proposed by Schubert & Barfknecht is thereby excluded.     

Thermal [1, 3] benzoyl migration in 1-(α-benzoyloxyarylideneamino)-1,2,3-triazoles. Part II

1-(α-Benzoyloxyarylideneamino)-4, 5-dirnethyl-1,2,3-triazoles (V) were prepared by reacting the sodium salt of substituted 1-benzoylamino-4, 5-dimethyl-1,2,3-triazoles (IV) with benzoyl chloride at ?50°. The uncatalyzed thermal isomerization of isoimides V to the corresponding imides VI was studied kinetically and the reaction mechanism is discussed.     

Synthesis,free-radical polymerization,and stereochemical configuration of methyl α-p-cyanobenzylacrylate

Methyl α-p-cyanobenzylacrylate was synthesized from dimethyl malonate following well-known organic reactions. The purified monomer was polymerized by a free-radical mechanism in benzene solution, using AIBN as initiator in the interval 50–90°C. The kinetic results seem to indicate an apparent ceiling temperature near 90°C. The analysis by ¹³C-NMR of polymers obtained indicates that the macromolecular chains are predominantly syndiotactic and the tacticity is independent of the polymerization temperature in the experimental interval studied. However, the determination of conditional probabilities for iso- and syndiotactic additions and the persistence ratios indicate that the propagation mechanism for the radical polymerization of methyl α-p-cyanobenzylacrylate does not follow a typical Bernoullian statistics.     

β-Cleavage of Bis(homoallylic) Potassium Alkoxides. Preparation of 3-Hydroxypropyl and 4-Hydroxybutyl Propenyl Ketones from γ- and δ-Lactones. Synthesis of (±)-Rose oxide

Starting from γ- and δ-lactones 1 – 3 , a two-step preparation of 3-hydroxypropyl and 4- hydroxybutyl propenyl ketones 10 – 18 is described, involving as the key step the β-cleavage of the bis(homoallylic) potassium alkoxides 4a – 9a . The novel methodology is illustrated by a short synthesis of (±)-rose oxide( 20 ).     

The Synthesis of (S)-(+)-2-Amino-3-(1-adamantyl)-propionic Acid (L-(+)-Adamantylalanine,Ada) as a ‘Fat’ or ‘Super’ Analogue of Leucine and Phenylalanine

Because of its overall steric resemblance to the phenylalanine analogue, carboranylalanine, the title compound was prepared by the modified Strecker synthesis of Patel & Worsley. The use of (S)-(?)-α-methylbenzylamine in the synthesis, the positive trend of [α]_D with increasing protonation, and the thin-layer chromatographic behaviour of synthetic diastereomeric dipeptides are strong indications that the configuration at the asymmetric carbon atom is S (natural L ). Its optical purity was ascertained by purification via the quinine and ephedrine salts of t-butoxy-carbonyl-adamantylalanine. The new amino acid shall be used for studies of structure-activity relationships of phenylalanine and leucine residues in biologically active peptides. In addition, a convenient synthesis in excellent yield of the starting material, 2-(1-adamantyl)-ethanal, by Pfitzner-Moffat oxidation of 2-(1-adamantyl)-ethanol is described.