Stereoselective synthesis and absolute configuration of the C33-C42 fragment of symbiodinolide

Cross-metathesis of methyl ester which was prepared from symbiodinolide with ethylene was performed to give the C33-C42 degraded fragment. This fragment was estimated to be (36S,40S)-diol by the modified Mosher method. Stereoselective synthesis of the (36S,40S)-diol and its diastereomer (36R,40S)-diol was achieved from l-aspartic acid. Synthetic bis-(S)- and (R)-MTPA esters which were derivatized from the (36S,40S)-diol exhibited spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded product. Thus, the absolute stereochemistry of the C33-C42 fragment was elucidated to be (36S,40S).     

Preparation and temperature-dependent enantioselectivities of homochiral phenolic crown ethers having aryl chiral barriers: thermodynamic parameters for enantioselective complexation with chiral amines

Homochiral crown ether (S,S)-1 containing 1-naphthyl groups as chiral barriers together with the phenol moiety was prepared by using (S)-3 as a chiral subunit which was resolved in enantiomerically pure form by lipase-catalyzed enantioselective acylation of (±)-3. Homochiral phenolic crown ether (S,S)-2, containing phenyl groups as chiral barriers, was also prepared from (S)-5 which was derived from (S)-mandelic acid. The association constants for their complexes with chiral amines in CHCl₃ were determined at various temperatures by the UV–visible spectroscopic method demonstrating that the crown ethers (S,S)-1 and (S,S)-2 displayed the large Δ_R−SΔG values of 6.2 and 6.4 kJ mol⁻¹, respectively, towards the amine 21 at 15°C. Thermodynamic parameters for complex formation were also determined and a linear correlation between TΔ_R−SΔS and Δ_R−SΔH values was observed.     

Synthesis and properties of S,R-alternating octinaphthalenes

(S,R,S,R,S,R,S)- and (S,R,S,S,S,R,S)-octinaphthalenes were synthesized by oxidative coupling of (S,R,S)-quaternaphthalene, and differences due to axis chirality of (S,R,S,R,S,R,S)-, (S,R,S,S,S,R,S)-, (S,S,S,R,S,S,S)-, and (S,S,S,S,S,S,S)-octinaphthalenes were compared using the R_f values on TLC, specific optical rotations, ¹H NMR chemical shifts of the hydroxy groups, and CD spectra. A clear CD additivity was found in the Δ? values of the ¹L_a transition around 290 nm, which are proportional to the difference between the numbers of S and R binaphthalene units.     

Chiral synthesis of (2s,3s,7s)-3,7-dimethylpentadecan-2-yl acetate and propionate,potential sex pheromone components of the pine saw-fly neodiprion sertifer (geoff.)

A synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-yl acetate ($\text{2}$) and propionate ($\text{3}$) is described. (2S)-2-Methyldecan-1-yl lithium ($\text{5}$) was reacted with (3S,4S)-3,4-dimethyl-γ-butyrolactone ($\text{6}$) to yield the ketoalcohol $\text{19}$ which upon Huang-Minlon reduction furnished (2S,3S,7S)-3,7-dimethylpentadecan-2-ol ($\text{1}$). Acylations gave the esters $\text{2}$ and $\text{3}$. The (2S)-2-methyldecan-1-yl lithium was obtained via asymmetric synthesis. The chiral lactone $\text{6}$ was obtained from (2S,3S)-trans-2,3-epoxybutane and dimethyl malonate.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

Reduced collagen cross links: the first synthesis of all the possible (2S,2′S)-stereoisomers of 5-hydroxylysinonorleucine and of 5,5′-dihydroxylysinonorleucine in enantiomerically pure form

The paper reports the first enantioselective synthesis of all the possible collagen reduced cross links as described: (2S,2′S,5R)- and (2S,2′S,5S)-5-hydroxylysinonorleucine 3a and 3b, (2S,2′S,5R,5′R)-5,5′-dihydroxylysinonorleucine 4a, (2S,2′S,5R,5′S)-5,5′-dihydroxylysinonorleucine 4b and (2S,2′S,5S,5′S)-5,5′-dihydroxylysinonorleucine 4c. The Williams’ glycine template methodology was used both for the introduction of a stereogenic at the α-position and for an easy protection of the amino acidic functionalities during the synthesis of the dimeric amino acids.     

Chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate by a Merrifield resin-bound enantiomerically pure chiral dimethylpyridino-18-crown-6 ligand

Three novel chiral pyridino-18-crown-6 ligands (S,S)-1, (S,S)-2 and (S,S)-3 were prepared and (S,S)-1 was attached to a Merrifield resin. The resulting adsorbent (S,S)-5 was used as a chiral stationary phase in the chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate. Also, a new chiral pyridono-18-crown-6 ligand (S,S)-6, used for the synthesis of (S,S)-1 and (S,S)-2, was prepared in two different ways.     

Synthesis and crystal structures of the first C2-symmetric bis-aldimine NCN-pincer complexes of platinum and palladium

(S,S)-2,6-bis[(N-α-methylbenzyl)imino]phenylpalladium bromide was synthesised by oxidative addition of palladium(0) to (S,S)-1-bromo-2,6-bis[(N-α-methylbenzyl)imino]benzene. In contrast, (S,S)-2,6-bis[(N-α-methylbenzyl)imino]phenylplatinum chloride was synthesised by direct C-H activation from the reaction of potassium tetrachloroplatinate with (S,S)-1,3-bis[(N-α-methylbenzyl)imino]benzene. The X-ray crystal structures of both pincer complexes were obtained. Treatment of both complexes with silver hexafluoroanimonate gave effective but not stereoselective catalysts for a Michael reaction between methyl vinyl ketone and methyl 2-cyanopropanoate.     

An approach to an asymmetric synthesis of stemofoline

A stereoselective Mannich reaction between an (S)-tert-butylsulfinimine and methyl (S)-4-benzyloxy-3-methylbutanoate followed by treatment with acid and N-protection was used to prepare methyl (2R,3S)-2-[(S)-2-benzyloxy-1-methylethyl]-3-tert-butoxycarbonylamino-6-methylenedecanoate. This was taken through to methyl (4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-5-tert-butoxycarbonylamino-3,8-dioxododecanoate which on treatment with trifluoroacetic acid cyclised stereoselectively to give (1R,2S,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-tert-butoxycarbonyl-3-oxo-8-azabicyclo[3.2.1]octane, a potential precursor of stemofoline. Reduction and N-deprotection of this ketone gave (1R,2S,3R,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-azabicyclo[3.2.1]octan-3-ol the structure of which was confirmed by X-ray diffraction.     

Synthesis of four enantiomers of 2,3-di(N-Boc-amino)-1-hydroxypropylphosphonates

Enantiomerically pure diethyl (1S,2R)-, (1S,2S)-, (1R,2R)- and (1R,2S)-2,3-di(tert-butoxycarbonyl)amino-1-hydroxypropylphosphonates were synthesised from diethyl (1S,2R,1′S)-, (1S,2S,1′R)-, (1R,2R,1′S)- and (1R,2S,1′R)-[N-(1-phenylethyl)]-2,3-epimino-1-hydroxypropylphosphonates, respectively, via aziridine ring opening with neat TMSN₃ followed by hydrogenolysis in the presence of Boc₂O. A plausible mechanism for the aziridine ring opening in 2,3-epimino-1-hydroxypropylphosphonates involving the intermediate aziridinium ions was proposed. Significant differences in the rates of the aziridine ring opening between diastereoisomeric phosphonates (1S,2R,1′S) and (1S,2S,1′R) were rationalised taking into account different conformations of the 1-phenylethyl group in both diastereoisomers.     

An efficient approach to the synthesis of enantiomerically pure trans-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids

The synthesis of (1R,2S)- and (1S,2R)-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids was accomplished using different strategies. The (1R,2S)-stereoisomer could be efficiently obtained by the cyclopropanation of ethyl diethoxyphosphorylacetate with the cyclic sulfate derived from (S)-3-benzyloxy-1,2-propandiol as a key step. The (1S,2R)-stereoisomer was synthesized from a readily available (1S,5R)-3-oxabicyclo[3.1.0]hexan-2-on-1-phosphonate.     

Practical and highly stereoselective method for the preparation of several chiral arylsulfinamides and arylsulfinates based on the spontaneous crystallization of diastereomerically pure N-benzyl-N-(1-phenylethyl)-arylsulfinamides

A novel and simple process for the preparation of enantiomerically pure (S_S)-benzenesulfinamide (S_S)-3a, (S_S)-p-toluenesulfinamide (S_S)-3b, (S_S)-p-chloro-benzenesulfinamide (S_S)-3c and (S_S)-p-fluorobenzenesulfinamide (S_S)-3d has been developed. The treatment of arylsulfinyl chlorides with (R)-N-benzyl-1-phenylethanamine in the presence of excess triethylamine gave diastereomeric mixtures of N-benzyl-N-(1-phenylethyl)-arylsulfinamides 1, which underwent spontaneous crystallization to furnish diastereomerically pure (R,S_S)-N-benzyl-N-(1-phenylethyl)-arylsulfinamides (R,S_S)-1a-1d in 28%, 29%, 27% and 31% yields, respectively. The diastereomerically pure compounds (R,S_S)-1 were then converted into four enantiopure (R_S)-methyl arylsulfinates (R_S)-2, and finally into four enantiopure (S_S)-arylsulfinamides (S_S)-3 in good yields.     

Synthesis of the ABC-ring models of goniodomin A: preference for the unnatural configuration at C11 of the BC-ring in a non-macrocyclic model system

To confirm the natural relative stereochemistry of the ABC-ring of goniodomin A (1), the corresponding three stereoisomeric compounds, (2R,5S,6S,7S,9S,11R,15S)-, (2R,5S,6S,7R,9R,11S,15R)-, and (2R,5S,6S,7R,9R,11R,15S)-isomers (2, 3, and 5, respectively), were stereoselectively synthesized using a Nozaki-Hiyama-Kishi reaction as a key step. It was also found that a (2R,5S,6S,7R,9R,11S,15S)-isomer (4), corresponding to the absolute configuration of 1 recently proposed by Sasaki, was not detected during the formation of 5 from a common ketodiol substrate under acid-catalyzed spiroacetalization conditions. This would be attributable to the absence of a macrocyclic framework.     

Synthesis of all the stereoisomers of 6-methyl-2-octadecanone, 6,14-dimethyl-2-octadecanone, and 14-methyl-2-octadecanone, the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma

All of the stereoisomers of the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma, were synthesized. They are (R)- and (S)-6-methyl-2-octadecanone, (6R,14R)-, (6R,14S)-, (6S,14R)-, and (6S,14S)-6,14-dimethyl-2-octadecanone, and (R)- and (S)-14-methyl-2-octadecanone. Enantiomers of citronellal and methyl (S)-3-hydroxy-2-methylpropanoate were the starting materials, and olefin cross metathesis was employed as the key reaction.     

Corrigendum to “Absolute configurations of griseorhodins A and C” [Tetrahedron Lett. 58 (50) (2017) 4721–4723]

The known antibiotic and cytotoxic compounds griseorhodin A (1) and griseorhodin C (2) were produced in solid culture by Streptomyces puniceus AB10, which was isolated from the leaf-cutter ant Acromyrmex rugosus rugosus. Their absolute configurations were unambiguously established as 6S,6aS,7S,8S and 6R,6aS,7S,8R, respectively, using vibrational circular dichroism (VCD) and density functional theory (DFT) calculations.     

Stereoselective synthesis of (3S,4R)-3,4-dimethyl-(S)-glutamine and the absolute stereochemistry of the natural product from papuamides and callipeltin

(3S,4R)-3,4-Dimethyl-(S)-glutamine, a common component of cyclodepsipeptides, papuamide A and callipeltin A, was stereoselectively prepared from (S)-pyroglutamic acid. The stereostructure of natural dimethylglutamine was unambiguously confirmed to be (2S,3S,4R) by comparison of the CD and NMR spectra of the synthetic 3,4-dimethylpyroglutamic acid with the hydrolysate of callipeltin A.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Biocatalytic and chemical routes to all the stereoisomers of methionine and ethionine sulfoxides

Biotransformations of the N-phthaloyl derivatives of d- and l-methionine and of d- and l-ethionine by Beauveria bassiana ATCC 7159 or Beauveria caledonica ATCC 64970 produce the corresponding (S_S) sulfoxides in good yield and diastereomeric excess. Pure (S_SS_C) diastereomers can be obtained from l-series substrates by crystallisation of the biotransformation extract, and the corresponding (S_SR_C) products obtained from d-series substrates by chromatography of the biotransformation extract. Hydrogen peroxide-catalysed oxidation of the N-phthaloyl derivatives of d- and l-methionine and of d- and l-ethionine gives diastereomeric mixtures from which the (S_SS_C) and (R_SR_C) diastereomers can be obtained by crystallisation, and the (S_SR_C) and (R_SS_C) diastereomers obtained by chromatography. N-Cbz- and N-t-Boc methionines are also converted to sulfoxides with predominant (S_S) configuration by both B. bassiana and B. caledonica, but the isolated yields and d.e. of products were generally lower than those obtained from the N-phthaloyl substrates.Removal of the N-phthaloyl group from diastereomerically pure methionine and ethionine sulfoxides gave the corresponding amino acid sulfoxides in high yield; removal of N-Cbz and N-t-Boc groups from protected methionine sulfoxides was also achieved without loss of configuration at sulfur.     

Stereoselective synthesis of 3-deoxy-piperidine iminosugars from l-lysine

A new method using electrochemical oxidation and/or OsO₄ oxidation has been used for the stereoselective synthesis of 2,3,6-trihydroxylated (5S)-piperidine derivatives. The electrochemical method was successively used for the conversion of N-protected piperidines to N-protected 1-methoxypiperidines and for the conversion of 2,3-didehydro-1-methoxypiperidine derivatives to 2,3-trans-1,2,3-triacetoxypiperidine derivatives. These triacetates were easily transformed into (2S,3S)-6-triacetoxy-(5S)-methylpiperidine and (2R,3R)-6-triacetoxy-(5S)-methylpiperidine. In addition, the 2,3-cis-dihydroxylation of 2,3-didehydro-1-methoxypiperidine derivatives with OsO₄ afforded (2R,3S)-6-triacetoxy-(5S)-methylpiperidine and (2S,3R)-6-triacetoxy-(5S)-methylpiperidine.     

Synthesis of oligomers including eight P-chiral centers and the construction of the 12-phosphacrown-4 skeleton

The stepwise oxidative coupling reaction from (S,S)-1 gave optically active oligomers, (S,R,R,S)-2 and (S,R,S,R,R,S,R,S)-3, having four and eight chiral phosphorus atoms, respectively. The behaviors of these oligomers in the solid state and in solution were investigated in detail. The first construction of a 12-phosphacrown-4 skeleton was also reported.