Biomimetic reactions of germacrenes

The biomimetic reactions of epoxygermacrene-D ($\text{1}$) with basic alumina afforded three new interesting compounds ($\text{4}$, $\text{5}$, and $\text{6}$), two of which ($\text{4}$ and $\text{6}$) have the same carbon skeleton as that of periplanone-A ($\text{3}$), a sexual stimulant for the American cockroach. The remaining one ($\text{5}$) is a bicyclo[3.1.0]hexane derivative, from whch an axisonitrile-3 type compound ($\text{14}$) has been produced. Finally, preisocalamendiol ($\text{2}$) was also converted into $\text{6}$.     

Biomimetic reactions of some macrocyclic diterpenes

Some macrocyclic diterpenes derived from euphohelioscopin A and euphornin have been stereoselectively converted into the jatropholane- and daphnane-type compounds and the known tricyclic compound which has been treated with phCOCl - pyridine to afford euphohelionone, the new type of diterpene isolated from euphorbia helioscopia L.     

Biomimetic monoacylation of diols in water. Lanthanide-promoted reactions of methyl benzoyl phosphate

The direct monoacylation of diols by acyl phosphate monoesters in water is a biomimetic analogy to the enzymic aminoacylation of tRNA by aminoacyl adenylates. Without catalysis, acyl phosphate monoesters react rapidly with amines but very slowly with water and alcohols. Lanthanide ions dramatically and selectively facilitate the base-catalyzed monoacylation of diols in water by methyl benzoyl phosphate (MBP), a typical acyl phosphate monoester, in neutral solutions where reactive amines are protonated and unreactive. The reaction patterns and reactivity of various diols with MBP in the presence of lanthanides are consistent with a mechanism that involves internal addition from the conjugate base of the bis-bidentate complex of the lanthanide with the diol and MBP. The method is also applicable to reactions of nucleosides as evidenced by the selective monoacylation of the 2'- or 3'-hydroxyl group of adenosine, without reaction of the 5'-hydroxyl group or the 6-amino group. Analogues of adenosine without the diol are unreactive. This suggests that the method will selectively monoacylate the hydroxyl groups at the unique diol in tRNA that forms the 3'-terminus.     

Biomimetic oxidation reactions of a naked manganese(V)-oxo porphyrin complex

The intrinsic reactivity of a manganese(V)-oxo porphyrin complex, a typically fleeting intermediate in catalytic oxidation reactions in solution, has been elucidated in a study focused on its gas-phase ion-chemistry. The naked high-valent Mn(V)-oxo porphyrin intermediate 1 ([(tpfpp)Mn(V)O](+); tpfpp=meso-tetrakis(pentafluorophenyl)porphinato dianion), has been obtained by controlled treatment of [(tpfpp)Mn(III)]Cl (2-Cl) with iodosylbenzene in methanol, delivered in the gas phase by electrospray ionization and assayed by FT-ICR mass spectrometry. A direct kinetic study of the reaction with selected substrates, each containing a heteroatom X (X=S, N, P) including amines, sulfides, and phosphites, was thus performed. Ionic products arising from electron transfer (ET), hydride transfer (HT), oxygen-atom transfer (OAT), and formal addition (Add) may be observed, with a predominance of two-electron processes, whereas the product of hydrogen-atom transfer (HAT), [(tpfpp)Mn(IV)OH](+), is never detected. A thermochemical threshold for the formation of the product radical cation allows an evaluation of the electron-transfer ability of a Mn(V)-oxo complex, yielding a lower limit of 7.85 eV for the ionization energy of gaseous [(tpfpp)Mn(IV)O]. Linear free-energy analyses of the reactions of para-substituted N,N-dimethylanilines and thioanisoles indicate that a considerable amount of positive charge is developed on the heteroatom in the oxidation transition state. Substrates endowed with different heteroatoms, but similar ionization energy display a comparable reaction efficiency, consistent with a mechanism initiated by ET. For the first time, the kinetic acidity of putative hydroxo intermediates playing a role in catalytic oxidations, [(tpfpp)Fe(IV)OH](+) and [(tpfpp)Mn(IV)OH](+), has been investigated with selected reference bases, revealing a comparatively higher basicity for the ferryl, [(tpfpp)Fe(IV)O], with respect to the manganyl, [(tpfpp)Mn(IV)O], unit. Finally, the neat association reaction of 2 has been studied with various ligands showing that harder ligands are more strongly bound.     

Biomimetic syntheses of ineleganolide and sinulochmodin C from 5-episinuleptolide via sequences of transannular Michael reactions

Treatment of a solution of the macrocyclic norcembranoid 7 with lithium hexamethyldisilazide in THF at −78 °C to 0 °C, leads to the polycyclic norcembranoids ineleganolide 1 and sinulochmodin C (2) (65%), which are found in the corals Sinularia inelegans and Sinularia lochmodes, respectively. The conversions are believed to be biomimetic, and occur by successive transannular Michael reactions in 7. Under different temperature conditions the novel polycycle 30 is the main product, alongside small quantities of 1 and 2. The polycycle 30 is possibly produced from ineleganolide 1, following a reverse oxy-Michael reaction and two successive aldol reactions. The significance of the synthesis of ineleganolide 1, sinulochmodin C (2) and the structure 30 from 5-episinuleptolide 7, to the likely biosynthesis of the related norcembranoids scabrolide A (3), scabrolide B (4) and horiolide 31 found in Sinularia sp. is discussed.     

Biomimetic selectivity

Synthetic organic chemistry normally achieves selectivity by manipulation of the intrinsic reactivity of the substrate, but enzyme use is quite a different principle. The geometry of the enzyme-substrate complex determines enzymatic selectivity, completely overwhelming any normal selective reactivities. Biomimetic chemistry aims to imitate the enzymatic style. Some early approaches used attached reagents or templates to direct photochemical and free radical processes, with a combination of geometric and reactivity control. Recent work uses a mimic of the enzyme class cytochrome P-450 to achieve the selective hydroxylations of steroids with complete domination by the geometry of the catalyst-substrate complex.     

Biomimetic synthesis of hyperolactones

Through a biomimetic pathway, hyperolactone D, 4-hydroxyhyperolactone D, and hyperolactone C were synthesized from methyl acetoacetate via Weiler's dianion method, asymmetric allylic alkylation, biomimetic lactonization, oxidation, and cyclization. The stereochemistry of the quaternary carbon was controlled efficiently by Palladium-catalyzed asymmetric allylic alkylation. This strategy was also used for the synthesis of hyperolactone B.     

Biomimetic synthesis of lantibiotics

The lantibiotics are a class of highly posttranslationally modified small peptide antibiotics containing numerous lanthionine and dehydroamino acid residues. We have prepared peptides containing multiple dehydroamino acids and cysteine residues in order to probe the biomimetic synthesis of the lantibiotics from their precursor peptides. A novel synthetic methodology was developed to allow the synthesis of multiple dehydroamino acid containing peptides. Cyclisations were rapid, quantitative and regiospecific. Remarkably the peptide sequences alone appear to contain sufficient information to direct a series of stereo- and regiospecific ring closures. Thus both the two linear peptides for the B and E-rings closed stereoselectively. In the case of the A-ring precursor peptide which contained two dehydroamino acids, cyclisation was again totally regioselective, although not totally stereoselective.     

Biomimetic Polyene Cyclizations

Certain polyenic substances having trans olefinic bonds in a 1,5 relationship can be induced to undergo stereospecific, non-enzymic, cationic cyclization to give polycyclic products with all-trans (“natural”) configuration. These transformations appear to mimic in principle the biogenetic conversion of squalene into polycyclic triterpenoids. Acetal and allylic alcohol functions are effective initiators for these cyclizations, and methylacetylenic end groups are particularly useful terminators since they lead to five-membered rings. Thus a tetraenic acetal having no chiral centers has been converted in a single step into a tetracyclic product having seven such centers. The process is highly stereoselective, giving only two of 64 possible racemates. Systems have also been developed for effecting the total synthesis of the steroid nucleus in a single step starting from a substrate containing only one ring. The mechanism of these biomimetic cyclizations and also that of their enzymic counterparts is still unknown, but the balance of the evidence favors a synchronous process.     

Biomimetic synthesis of diversifolin

The conversion of a germacranolide structure (tagitinin C) into a furanoheliangolide one (diversifolin) was achieved by hydride conjugate addition using Stryker’s reagent.     

Biomimetic condensation copolyesters

Copolyterephthalates of bis(4-hydroxy-3-methylphenyl)-2,2-propane and N-methyldiethanolamine and their hydrochloric salts of various compositions and microstructures have been prepared by the copolycondensation of hydrophilic and hydrophobic comonomers. It has been shown that the transition from random proteinlike structures to the block structures makes it possible to preserve biomimetic properties of the copolymers at a smaller content of charged units in macromolecules. The ability of charged polymers to survive in aqueous solutions has been used for the synthesis of copolyterephthalate of N-bis(hydroxyethyl)tetradecylmethylammonium bromide and N-methyldiethanolamine demonstrating fungicidal activity.     

Biomimetic chemistry of xylomollin

Kingiside aglucon ($\text{2}$$\text{b}$) undergoes stereoselective addition of CH₃OH to its C(3,4) enol ether double bond to give a C(1,3,9) diastereomer of xylomollin ($\text{1}$), a secoiridoid aglucon that has insect antifeedant properties.     

Biomimetic syntheses of syncarpurea

Simple syntheses of syncarpurea (1) from syncarpic acid and the amino acids ornithine or citrulline are presented.     

Biomimetic synthesis of the shimalactones

A biomimetic synthesis of shimalactone A and B is described. Its key features are an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a Stille coupling/8pi-6pi electrocyclization cascade to create the oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis is convergent and void of protecting groups.     

Biomimetic synthesis of leukotriene A

A biogenetically patterned conversion of $\text{1}$ into $\text{2}$ is described. This transformation has been found to be non-stereospecific with respect to the geometry of the newly generated double bond at C9(10).