Total synthesis of the phytotoxic stagonolides A and B

The chemo-enzymatic and covergent synthesis of stagonolide B and the synthesis of stagonolide A, a phytotoxic 10-membered lactone have been achieved starting from d-ribose with overall yields of 25% and 8.7%, respectively. The synthesis contained simple steps in developing three centers’ key intermediates, namely the enzymatic (Novozyme-435) resolution of a propargylic alcohol followed by macrolactonization and RCM.     

The total synthesis and structural revision of stagonolide D

The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant -OTBS deprotection and displacement of an -OMs placed next to it, resulting in the formation of the epoxide ring.     

Stereoselective synthesis of revised structure of stagonolide G

A concise total synthesis of the revised structure of stagonolide G has been achieved in 11 steps and with an overall yield of 31.7%. Key reaction sequence includes BAIB/TEMPO mediated tandem oxidation and lactonization, Lindlar’s hydrogenation, regioselective epoxide opening by an in situ generated alkynyl as nucleophile, Sharpless asymmetric dihydroxylation, and Jacobsen kinetic resolution.     

First stereoselective total synthesis of stagonolide G

First stereoselective total synthesis of nonenolide stagonolide G involving a convergent strategy is described. The key reactions include Keck allylation and Grubbs ring closing metathesis reaction.     

Asymmetric Total Synthesis of Stagonolide G

A simple asymmetric total synthesis of stagonolide G ( 1 ) is described. Asymmetric dihydroxylation, regioselective epoxide ring opening, and vinyl Grignard reactions are involved in generating the stereogenic centers C(4) and C(8), followed by Grubbs‐II‐catalyzed ring‐closing metathesis (RCM).     

An alkaloid of Dioscorea hispida, Dennstedt–IV Further investigations on the lactose ring

Reductive degradation of the lactone ring of dioscorine has yielded a saturated tertiary alcohol, the formation of which means that the previously proposed formula (I) for the alkaloid is incorrect. The lactone and tropane systems are linked in a spiro manner, as in (VI) or (VII), of which the former is preferred for dioscorine. The behaviour of the alkaloid on Hofmann degradation can be explained on the basis of structure (VI). From infra-red studies on the above tertiary alcohol dioscorine is derived from 7-hydroxytropane, and the (–)-base is therefore (XX) or its optical enantiomorph.     

The imidato-alkenyllithium route for the synthesis of the isoquinocycline-pyrrolopyrrole substructure

A convergent and effective synthesis of the pyrrolopyrrole substructure (CDEFG) of the isoquinocyclines is reported. A key step is a tin-lithium exchange of an imidato-alkenyltin compound (a ring G equivalent) and the subsequent acylation with a lactone. The resulting acetal is used successfully for the ring F closure to the pyrrolopyrrole. The sole formation of the isoquinocycline N,O-acetal epimer is in accordance with the proposed mechanism for the isomerization of quinocyclines to isoquinocyclines.     

Anthecularin: a novel sesquiterpene lactone from Anthemis auriculata with antiprotozoal activity

Anthecularin (1), a minor sesquiterpene lactone with a novel ring system was isolated from Greek Anthemis auriculata (Asteraceae). Its structure was elucidated by means of NMR, HRMS, and X-ray crystallography. Anthecularin showed antitrypanosomal (IC50=10.1 microg/mL) and antiplasmodial activity (IC50=23.3 microg/mL) and inhibited two key enzymes of the plasmodial type II fatty acid biosynthesis pathway, PfFabI and PfFabG (IC50 values=14 and 28.3 microg/mL, respectively). A probable biogenesis of 1 is also proposed and discussed.     

A new phenolic lactone from the bark of Phellodendron chinense

A new phenolic lactone,named phellolactone(1) was isolated from the bark ofPhellodendron chinense Schneid and its structure was elucidated by means of extensively spectroscopic methods,including IR,UV,HRESI-MS and NMR techniques.     

Two novel lanostane triterpenoids from Ganoderma sinense

Two novel lanostane-type triterpenes, Ganolactone B and Ganoderiol A triacetate, were isolated from the fruiting bodies of G. sinense, together with six known compounds. The structures of the two new triterpenes were determined as 3beta,7beta- dihydroxy-11,15-dioxo-lanosta-8-en-24-->20 lactone (1) and 3beta,24,26-triacetoxy-5alpha-lanosta-7,9(11)-dien-25-ol (2), respectively, by chemical and spectroscopic means.     

Solid-phase synthesis and spectroscopic studies of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline.

An efficient solid-phase synthesis of the TRH analogue Glp-His(Nim-Trt)-Hyp-OH is described. Na-Fmoc protected amino acids and DCC/HOBt activation were employed. The bulky and mild-acid-sensitive 2-chlorotrityl resin, utilised as the solid support, completely suppressed dioxopiperazine formation. The tripeptide is a key intermediate in the synthesis of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline. The tripeptide was converted, with inversion of configuration at C-4 of the Hyp residue, to Glp-His(Nim-Trt)-cHyp lactone in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD). One-pot MeOH-TPP-DEAD transesterification of the lactone, followed by Nim-detritylation, provided Glp-His-cHyp-OMe. This ester gave the corresponding amide and acid on ammonolysis and saponification, respectively. A high-field 1H NMR investigation of Glp-His-cHyp-OH and its diastereomer Glp-His-Hyp-OH, obtained by Nim-detritylation of the key tripeptide, showed that the configuration at C-4 of the prolyl residues is critical for the determination of the preferred three-dimensional structure of the molecules.     

Thermodynamical properties of ε-caprolactone

The values of the combustion and enthalpies of formation for ε-caprolactone were determined by means of combustion calorimetry. The vapor pressures of lactone were measured in the range of 283–353 K, and the value of its enthalpy of vaporization was estimated by the transpiration method. Conformational analysis and calculations of the equilibrium structures, inertia moments, and sets of fundamental vibrations was performed by the B3LYP/6-311++G(3 df, 3 pd) quantum-chemical method. The total energies of the most stable lactone conformers were found and Δ_fH(g) was estimated using the composite G3MP2 method. The set of fundamental vibrations for the most stable conformers of the compound was developed on the basis of the available experimental IR spectra and calculated vibration frequencies. The values of the thermodynamic properties of ε-caprolactone were determined in the ideal ga s state in the range of 0—1500 K. A set of reliable and interconsistent thermodynamic parameters for ε-caprolactone was created. Thermodynamic analysis for liquid-phase polymerization of s-caprolactone in the temperature range of 220—500 K was carried out.     

Stereoselective synthesis of anamarine

A stereoselective synthesis of the naturally occurring, α,β-unsaturated lactone anamarine is described. The key step was a highly stereoselective aldol reaction of a protected erythrulose derivative with a chiral aldehyde. Another relevant step was an asymmetric aldehyde allylation with a chiral allylborane. The lactone ring was made by means of a ring-closing metathesis.     

B-norsteroids from Hymenoscyphus pseudoalbidus

Two viridin-related B-norsteroids, B-norviridiol lactone (1) and B-norviridin enol (2), both possessing distinct unprecedented carbon skeletons, were isolated from a liquid culture of the ash dieback-causing fungus Hymenoscyphus pseudoalbidus. Compound 2 was found to degrade to a third B-norsteroidal compound, 1β-hydroxy-2α-hydro-asterogynin A (3), which was later detected in the original culture. The proposed structure of 1 is, regarding connectivity, identical to the original erroneous structure for TAEMC161, which was later reassigned as viridiol. Compound 2 showed an unprecedented 1H-13C HMBC correlation through an intramolecular hydrogen bond. The five-membered B-ring of compounds 1-3 was proposed to be formed by a benzilic acid rearrangement. The known compound asterogynin A was found to be formed from 3 by a β-elimination of water. All compounds were characterized by NMR spectroscopy, LC-HRMS and polarimetry.     

Methyl 1,2‐Shift Rearrangement on C‐ring and Decarboxylation at C28 of Oleanolic Acid Derivatives

A new oleanolic acid derivative with A‐ring lactone, C‐ring rearrangement and decarboxylation at C28 was synthesized, which was confirmed by HRMS, NMR and X‐ray crystal structure. It is the first report about the methyl rearrangement on C‐ring of oleanolic phenylmethyl ester, and the possible mechanism was proposed as the 1,2‐methyl shift.     

A carbon-centered radical unreactive toward oxygen: unusual radical stabilization by a lactone ring

A lactone ring confers unusual stability to a diphenylmethyl-like radical that is virtually unreactive toward oxygen. Thus, the radical derived from HP-136 is about 10,000 times less reactive than typical carbon-centered radicals. A reversible reaction with oxygen is proposed by analogy with triphenylmethyl; however, the association constant is about 1000 times smaller for HP-136 than for triphenylmethyl. While the lactone ring greatly influences the reactivity, the spectroscopy of the HP-136-derived radical is in line with that expected for a substituted diphenylmethyl radical.     

A New Dimeric Stilbenoid with a Five‐Membered Lactone Ring from Shorea hemsleyana

From the stem bark of Shorea hemsleyana, a new dimeric stilbenoid with a five‐membered lactone ring, shorealactone ( 1 ) was isolated. The absolute configuration was determined by means of 2D NMR techniques and X‐ray crystal‐structure analysis of its 4‐bromobenzoyl derivative 1e by means of anomalous scattering of the Br‐atom.     

Synthesis of stagonolide C from Mulzer epoxide

Total synthesis of stagonolide C using chiral pool strategy is described. The two key intermediates were prepared from l-glutamic acid and d-glucono-1,5-lactone, followed by Julia-Lythgoe olefination and Yamaguchi esterification to afford the target compound in an efficient way.     

Stereoselective Total Synthesis of Botryolide E and Ophiocerin C

A highly stereoselective approach to the total synthesis of the γ‐lactone derivative botryolide E and tetrahydropyran derivative ophiocerin C via a common polyketide precursor by means of Prins cyclization and MacMillan α‐aminoxylation sequence is described. The method can conveniently be utilized for the preparation of further related γ‐lactone and tetrahydropyran derivatives.