Synthesis of chiral tripeptides by asymmetric hydrogenation of dehydrotripeptides. Remarkable effects of N-protecting groups on stereoselectivity and reactivity

Dehydrotripeptides, X-$\text{C}\text{*}$CH(Rⁱ)-ΔPhe-$\text{C}\text{*}$CH(R^k)COOMe ($\text{3}$: X = ^tBOC-NH,CBZ-NH, CF₃CONH and N₃), were employed for the asymmetric hydrogenation catalyzed by chiral rhodium complexes and it was found that ^tBOC-$\text{3}$ brought about by far the best results. Stereoselective dideuteration of a ^tBOC-$\text{3}$ was successfully performed.     

Isolation and structural elucidation of heliangolidin,a new sesquiterpene lactone from artemisia canariensis

A new heliangolide has been isolated from aerial parts of $\text{Artemisia canariensis}$, and identified as (6$\text{E}$,10$\text{Z}$)(3$\text{S}$,3a$\text{R}$,4$\text{S}$,lla$\text{R}$)-3a,5,8,11a--tetrahydro-4-acetoxy-3,6, 1O-trimethyl-2,9 (3$\text{H}$, 4$\text{H}$) -cyclodeca[b] furandione. The structural elucidation of the new compound, named heliangolidin, was carried out by spectral means (MS, IR, ¹H and ¹³C NMR, and two dimensional ¹H-¹³C chemical shift correlations) and X-ray diffraction analysis.     

Studies on amino acids and peptides VIII : Synthesis and crystal structure of two monothiated analogues of Boc-Gly-S-Ala-Aib-OMe

The model tripeptide Boc-Gly-S-Ala-Aib-OMe ($\text{2b}$) and the two monothiated analogues Boc-Gly(¹ψ²CSNH)-S-Ala-Aib-OMe ($\text{2c}$) and Boc-Gly-S-Ala(²ψ³ CSNH)-Aib-OMe ($\text{2a}$) were synthesized. Peptide $\text{2a}$ was obtained by thiation of $\text{1a}$ using 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, Lawesson's Reagent (LR), followed by deprotection of the Boc group and coupling with Boc-Gly-OH. Thiation of $\text{2b}$ with LR regiospecifically transformed the protected tripeptide to the monothiated analogue $\text{2c}$. X-Ray diffraction analysis showed that the type-III β-turn formed by the reference peptide $\text{2b}$ is preserved in the monothiated analogue $\text{2a}$; conversely,the structure of the isomeric tripeptide $\text{2c}$ is partially extended.     

Synthesis of 13C and 15N labelled (S)-Tryptophan

(R,S)-serine-1-¹³C was incubated in a culture of $\text{Escherichia}$$\text{coli}$ cells to produce (S)-trytophan-1-¹³C. Bromoacetyl bromide-2-¹³C was converted to bromoacetanilide and cyclization of the anilide, followed by reduction and dehydrogenation furnished indole-3-¹³C. Indole-¹⁵N was synthesized by known sequences. These ¹³C and ¹⁵N isotomers of indole were converted by commercially available, lyophilized $\text{E}$. $\text{coli}$ to furnish (S)-tryptophan-γ-¹³C and (S)-tryptophan-indole-¹⁵N, respectively.     

Synthesis and NMR study of norbornane/norbornene-fused tetracyclic azetidinones

Tetracyclic azetidinones$\text{8}$,$\text{9}$ and $\text{12}$–$\text{17}$ were synthesized. In the cases of$\text{8}$ and$\text{9}$, the main component was isolated from the two-component product of the cycloaddition. The minor component was concentrated to give a mixture, from which a computer technique utilizing the known spectrum of the main component gave the proton resonance spectrum also of the minor component. Only one diastereomer could be isolated for the each of the analogues$\text{12}$–$\text{17}$. Reaction of the 1,3-oxazine $\text{3}$ with chloroacetyl chloride gave, besides the azetidinone $\text{12}$, the 1,3-oxazine [2,3-$\text{b}$]-1,3-oxazin-4-one derivative$\text{18}$. Configurations and conformations were determined by IR, ¹H and ¹³C NMR spectroscopy.     

Metabolites of Alternaria solani part V. Biosynthesis of altersolanol A and incorporation of altersolanol A-13Cx into altersolanol B and macrosporin

The biosynthesis of the tetrahydroanthraquinone, altersolanol A ($\text{1}$), by $\text{Alternaria solani}$ has been established by the incorporation of [1,2-¹³C₂]-acetate. A blocked culture of $\text{A. solani}$ was utilized to reveal that $\text{1}$ is metabolized to altersolanol B and macrosporin.     

Synthesis of Δ1-carbapenem derivative by aldol condensation method

The Δ¹-carbapenem derivative($\text{6}$) was prepared by the aldol condensation of the dialdehydic compound($\text{5}$) with piperidinium acetate. Careful hydride reduction followed by benzoylation gave $\text{7}$b, which was successfully decarbalkoxylated to $\text{8}$. The X-ray structure analysis of $\text{8}$ showed the C-3 carboxylate group and C-5 H are $\text{cis}$ each other.     

Synthesis and absolute configuration of +-lineatin,the pheromone of trypodendronlineatum

A new synthesis of (±), (+)- and (-)-lineatin (3,3,7-trimethyl-2, 9-dioxatricyclo [3.3.1.0^4,7] nonane, $\text{1}$) was achieved. The stereochemistry of (+)-lineatin was established as 1$\text{R}$, 4$\text{S}$, 5$\text{R}$, 7$\text{R}$ by an X-ray crystallographic analysis of an intermediate $\text{1}$$\text{5}$.     

A convenient route to carbocyclic analogs of nucleosides: (±) aristeromycin

Stereocontrolled elaboration of cyclopentadiene-azomethine adducts $\text{1}$⁶ and $\text{2}$⁷ led to a short total synthesis of (±) aristeromycin. In the course of this work a novel zinc reduction ($\text{6}$/$\text{7}$+$\text{9}$) was observed. Also, ozonolysis of the $\text{gem}$-dihalo olefin $\text{10}$ in methanol directly gave the methyl ester $\text{12}$.     

The synthesis and x-ray crystal structure of a tetracyclo[4.2.1.1.2,503,7]decane derivative. A rigid,twist boat-containing ring system.

Attempted intramolecular pinacolization of cage diketone $\text{4}$ unexpectedly gave ketol $\text{5}$ instead. Compound $\text{5}$ was shown to possess the rare tetracyclo[4.2.1.1.^2,50^3,7]decane ring system by means of an X-ray crystal structure of hydroxy-mesylate $\text{10}$ derived from $\text{5}$ by sodium borohydride reduction followed by mesylation. A possible mechanism for the transformation of $\text{4}$ into $\text{5}$ is presented, and certain noteworthy features of the crystal structure of $\text{10}$ are discussed. The base-catalysed fragmentation of $\text{10}$ to give enone $\text{11}$ is also described.     

The optical absorption and emission spectra of Cs2NaSmCl6

Optical absorption and emission spectra are reported for single crystals of the cubic elpasolite Cs₂NaSmCl₆. The variable temperature spectra obtained at high resolution are assigned using energies and relative intensities. Transitions from the ground level, ⁶H_{$\text{5}\text{2}$} to cystal fi levels of ⁶H_{$\text{7}\text{2}$-$\text{15}\text{2}$}, ⁶F_{$\text{1}\text{2}$-$\text{11}\text{2}$}, ⁴G_{$\text{5}\text{2}$-$\text{9}\text{2}$}, ⁴F_{$\text{3}\text{2}$,$\text{5}\text{2}$}, ⁴I_{$\text{9}\text{2}$}, and ⁶P_{$\text{3}\text{2}$, $\text{5}\text{2}$} are located and characterized. Intensity calculations are reported for magnetic dipole allowed transitions. The dominance of vibronic intensity in ⁶H_{$\text{5}\text{2}$}→⁶F _{$\text{1}\text{2}$-$\text{9}\text{2}$} and ⁶P_{$\text{3}\text{2}$, $\text{5}\text{2}$} transitions is accounted for qualitatively through the ligand polarization model involving quadrupole metal (Sm³⁺)-ligand (Cl^?) interaction mechanisms. The E_u″(⁶H_{$\text{5}\text{2}$})→E′(⁶H_{$\text{1}\text{2}$}) E_u′(⁶F_{$\text{1}\text{2}$}) no-phonon transition is postulated to be pure electric quadrupole allowed. The ground state magnetic moment is determined to be very small from magnetic circular dichroism (MCD) spectra.This study has led to the assignment of nearly all of the crystal field levels in the visible and IR region for Cs₂NaSmCl₆. A total of 27 such levels were identified, 17 from no-phonon transitions and the rest from vibronic transitions. The magnetic dipole intensity calculated using intermediate coupling O_h wavefunctions along with a crystal field analysis of the splitting pattern was used in the assignment of the levels. Vibronic bands were observed for all transitions and their vibrational symmetries were tentatively assigned. MCD data were used to determine the magnet moment of the ground state.     

An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mono—claisen rearrangement

A short, efficient approach to a key chiral intermediate for the synthesis of pseudomonic acids A and C is delineated.Pseudomonic acids A($\text{1a}$), B($\text{1b}$), and C($\text{2}$) are members of a novel of “C-glycopyranoside” antimicrobial agents which have recently attracted synthetic attetion.² Presently, we wish to report a short efficient stratedy towards the total synthesis of opticaly active pseudomonic acids. The sequence is highlighted by a novel controlled mono-Claisen rearrangement and a highly regioselective π-allylpalladium mediated displacement.Diacetyl-(L)-arabinal ($\text{3}$)³ was converted to the bis-ketenesilylacetal $\text{4}$ and warmed to 60°C according to the Ireland ester-enolate Claisen rearrangement method.⁴ Over a period of ≈5h, smooth conversion to a major rearranged product $\text{5}$ was observed by 300 MHz NMR. The identity of $\text{5}$ was confirmed by direct desilylation and methylation (KF, KHCO₃, H₂O, HMPA, CH₃I). After flash chromatography, compound $\text{7}$ was isolated in 55% overall yield from $\text{3}$. Careful inspection of the crude methylation product revealed the presence of ≈5% doubly rearranged product $\text{6}$.The rearrangement of $\text{4}$ to $\text{5}$ is a unique example of a selective mono-Claisen rearrangement in which the rate of a second similar Claisen rearrangement ($\text{5}$ → $\text{6}$) is much slower under the reaction conditions. Although the reasons for this interesting selectivity are unclear at this time,⁵ in practice, the mono-Claisen rearrangement obviates the need for selective differentiation of the two hydroxyl groups, a difficult task at best, in this case.Palladium mediated allylic acetate displacement provided an ideal method for introduction of a second chemodifferentiated side chain with allylic retention and retention of stereochemistry. Alkylation of $\text{7}$ with sodiothylmalonate using 5 mole % Pd(O)dppe₂⁶ was unusually facile (<45 min, 25°C, THF). After semi-preparative HPLC, essentially a single regio- and stereoisomer was isolated in 96% yield.⁷ Structure $\text{8}$ was confirmed by extensive ¹H-NMR decoupling, as well as an off-resonance ¹³C-NMR experiment. In particular, H₁ (δ 4.53) was coupled vicinally to H₆ and H₆′ (5 Hz, 8 Hz) and H₂ (1.5 Hz), and allylically to H₃ (2 Hz). In contrast, H₄ (δ 2.78) was coupled to H₇ (10 Hz), H_5e and H_5a (1.8 Hz, 4 Hz), H₃ (5 Hz), and H₂ (<1 Hz). In addition, H₁ and H₄ exhibited a small long range coupling constant (J = <1 Hz). The coupling constants rule out

regioisomer $\text{9}$ and are fully consistent with the indicated conformation, which minimizes 1,3-diaxial-like interactions.Finally, catalytic osmylation of $\text{8}{}^8$ gave a single cis-diol $\text{10}$ in nearly quantitative yield. Appending of suitably functionalized side chains to provide an enantiocontrolled synthesis of pseudomonic acids A($\text{1a}$) and C($\text{2}$) is in progress.^9,10     

Activation and transfer of oxygen XV evidence for the transient opening of the pyrazine ring in n1- and n5- alkylflavin models. 4a- to 1010- adduct isomerization and pyrazine- and pyrimidine- ring contractions.

The pyrazine ring opening is proven by rearrangements leading to benzimidazoles $\text{4}$, $\text{13}$ and $\text{14}$. A 4^a- to 10^a-adduct isomerization ($\text{6}$ → $\text{7}$) and the intermediacy of a carbonyl oxide $\text{15}$ are indicated by pyrimidine ring contractions into $\text{8}$ and $\text{9}$, respectively.     

Inept-29Si NMR study of a TiCl4-mediated reaction of an enol silyl ether

Condensation of 1,3-bis(trimethylsiloxy)-1-methoxybutadiene ($\text{1}$) and 2-phenyl-2,2-dimethoxyethanal ($\text{2}$) under TiCl₄ condition gave the γ-hydroxycyclopentenone product $\text{3}$. The reaction was followed by INEPT²⁹Si NMR. Implication to the mechanism of the reaction was discussed.     

Syntheses of gramicidin s analogs containing D-Serine or a dehydroalanine residue,and asymmetric hydrogenation of the dehydroalanine

Gramicidin S (GS) analogs, (D-Ser(Bzl)^4,4′]-GS ($\text{17}$), [D-Ser^4,4′]-GS ($\text{18}$), and [L-Orn(Boc)^2,2′,D-Ser^4,4′]-GS ($\text{19}$) were synthesized and $\text{17}$ showed high antibacterial activity. One residue of D-Ser in $\text{19}$ was converted asymmetrically to D-Ala via α,β-dehydroalanine.     

Chiral recognition of alkene and arene hydrocarbons by 1H and 13C NMR. determination of enantiomeric purity

Simultaneous presence of the salt $\text{1}$ and one of the lanthanide complexes (+)-$\text{2}$, (+)-$\text{3}$, or (+)-$\text{4}$ splits ¹H or ¹³C NMR signals of the chiral alkenes $\text{5}$, $\text{6}$, and $\text{8}$ as well as of the chiral arene $\text{7}$; the enantiomeric purity of a mixture of (+)- and (?)-$\text{8}$ was determined successfully.     

An NMR and theoretical study on the conformational behaviour of benzylidenemalonaldehydes : A conformationally flexible unsaturated system

The conformational behaviour of the methylenemalonaldehyde fragment of the title compounds is characterized by solvent and temperture dependencies of ¹J($\text{CH}$O), ³J($\text{C}$HO,C$\text{H}$O), ³J($\text{C}$HO,C$\text{H}$), ⁴J(C$\text{H}$O,C$\text{H}$O) and ⁴J(C$\text{H}$O,C$\text{H}$) spin-spin couplings as well some $\text{ab}$$\text{initio}$ (STO-3G) and semiempirical level Molecular orbital calculations. The conformational behaviour of the couplings is also discussed on the basis of some INDO/FPT calculations. The conformations of the two formyls are strongly correlated, the $\text{trans}$-$\text{cis}$ arrangements being favored. The conformation of the Z-formyl is determined by the steric interaction with the aromatic nucleus. The conformations of the formyls are sensitive to solvent and substitution on the aryl. Approximate populations and couplings of the sites are derived. There is some evidence about the non-planarity of the methylenmalonaldehyde fragnent. Complex formation with Mg(C10₄)₂ is reported.     

On the mode of incorporation of leucine samples labelled at positions 5 and 2 with 3H and 14C into the isoprenylated tryptophan derivative echinuline from aspergillusamstelodami

Feeding experiments with (4$\text{S}$) [5-³H;5-¹⁴C]$\text{L}$-leucine ($\text{1a}$) and with the (4$\text{S}$) [5-³H;2-¹⁴C]-isomer ($\text{1b}$) show that incorporation into the isoprenylated tryptophan derivative echinuline ($\text{3}$), produced by $\text{Aspergillus}$$\text{amstelodami}$, involves, to a large extent, loss of the fragment enbodying the carbon atom at position 2 of the fed amino acid.     

Synthesis of a tetracyclodecenone with two orthogonal π-electron systems via a 1,3-through cage elimination in a bridgehead substituted 1,3-bishomocubyl acetate

Stereoselective reduction of 1,3-bishomocubanone acetate $\text{1}$ followed by mesylation leads to an epimeric mixture of mesylates $\text{3}$. Base induced homoketonization of the anti-epimer $\text{3b}$ affords tetracyclo[5.3.0.0^2,5 O^4,8]decenone $\text{4}$.     

Temperature dependence of collisional deactivation of Tl(62P32)

The rate coefficients for the collisional deactivation of Tl(6²P_{$\text{3}\text{2}$}) by several gases has been determined at 300°K. This data is compared with that previously obtained at higher temperatures and the Arrhenius parameters calculated. Both the overall rate coefficients and temperature effects display trends similar to those observed for 1(5²P_{$\text{1}\text{2}$}) relaxation. The deactivation of Tl(6²P_{$\text{3}\text{2}$}) by O₂ is shown to proceed by a process involving an equilibrium with Tl(6²P_{$\text{1}\text{2}$}) and electronically excited oxygen, probably O₂(¹Δ_g).