Monooxygenase stereoselectivity in the biosynthesis of stereoisomeric spiroacetals in the cucumber fly,Bactrocera cucumis

[reaction: see text] The stereoselectivity of hydroxylation of alkyltetrahydropyran-2-ols (or their biological equivalents) in the formation of stereoisomers of 2,8-dimethyl-1,7-dioxaspiro[5.5]undecanes in male Bactrocera cucumis has been investigated. Racemic, (6R)-, and (6S)-6-methyl-2-[5-(2)H(1)]-n-pentyltetrahydropyran-2-ol was administered under an [(18)O(2)]-enriched atmosphere. The stereochemistry and isotopic composition of generated spiroacetals were monitored by combined enantioselective GC-MS. The monooxygenase(s) strongly prefers the (6S)-substrate and furnishes predominantly the (S)-alcohol and then the (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. The (2S,6S,8R) and (2R,6S,8S) (E,Z)-isomers appear to be derived in vivo predominantly from (R)-hydroxylation of the (6S)-tetrahydropyranol.     

(18)O]-oxygen incorporation reveals novel pathways in spiroacetal biosynthesis by Bactrocera cacuminata and B. cucumis

The origins of the oxygen atoms in 1,7-dioxaspiro[5.5]undecane (1) and hydroxyspiroacetal (2) from Bactrocera cacuminata, and in 2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (3) and hydroxyspiroacetal (4) from B. cucumis, have been investigated by incorporation studies from both [(18)O(2)]-dioxygen and [(18)O]-water. Combined GC-MS examination and high-field NMR analysis have demonstrated that all oxygen atoms in 1 and 2 from B. cacuminata are dioxygen derived, but in contrast, the spiroacetals 3 and 4 from B. cucumis incorporate one ring oxygen from water and one ring oxygen (and the hydroxyl oxygen in 4) from [(18)O(2)]-dioxygen. These results reveal not only the generality of monoxygenase mediation of spiroacetal formation in Bactrocera sp., but also an unexpected complexity in their biosynthesis. A general paradigm accommodating these and other observations is presented.     

Synthesis and absolute configuration of a constitutionally-new [5.6] spiroacetal from B. tryoni (Queensland fruit fly)

A novel spiroacetal, (2S,6R,8S)-2-methyl-8-ethyl-1,7-dioxaspiro[5.6]dodecane (1), has been identified from the volatile secretions of female B. tryoni by mass spectral analysis and synthesis of an authentic, enantioenriched sample.     

Spiroacetal biosynthesis: (+/-)-1,7-dioxaspiro[5.5]undecane in Bactrocera cacuminata and Bactrocera oleae (Olive Fruit Fly)

[reaction: see text] A biosynthetic scheme rationalizing the formation of (+/-)-1,7-dioxaspiro[5.5]undecane (5) in the fruit fly species Bactrocera cacuminata and Bactrocera oleae (olive fruit fly) is presented. Incorporation studies with deuterium-labeled keto aldehyde (10), 1,5-nonanediol (11), and 1,5,9-nonanetriol (12), and our previous finding that both oxygen atoms of 5 originate from dioxygen, are strongly evidentiary. The racemic condition of the natural spiroacetal 5 is accounted for, and inter alia, it is demonstrated that dihydropyran (18) is not an important intermediate en route to 5.     

Energetics of oxaspirocycle prototypes: 1,7-dioxaspiro[5.5]undecane and 1,7,9-trioxadispiro[5.1.5.3]hexadecane

The relative gas-phase energetics of several low-lying isomers of 1,7-dioxaspiro[5.5]undecane and 1,7,9-trioxadispiro[5.1.5.3]hexadecane have been calculated with second-order Mller-Plesset perturbation theory and basis sets as large as aug-cc-pVQZ. Relative energies in THF, dichloromethane, acetone, and DMSO have been estimated with corrections from polarized continuum model calculations at the B3LYP/6-311+G(d) level. In the most stable conformation of 1,7-dioxaspiro[5.5]undecane, both rings adopt chair conformations, and both oxygens are axially disposed (2A). It is more than 2 kcal mol(-1) more stable than all the other conformers. In agreement with previous work, the "twist-boat" trans isomer (3A) is the most stable isomer of 1,7,9-trioxadispiro[5.1.5.3]hexadecane. However, in contrast to this earlier study, an "all-chair" conformation (3B) is found to be the most stable cis isomer of 1,7,9-trioxadispiro[5.1.5.3]hexadecane (E approximately 0.5 kcal mol(-1) in acetone and DMSO). Gauge-independent atomic orbital computations at the B3LYP/6-311+G(d) level indicate that this is the only cis isomer with (13)C NMR chemical shifts that are qualitatively consistent with the experimental spectra.     

Synthesis of Chiral Spiroacetals from Carbohydrates

Chiral spiroacetals of the 1,7-dioxaspiro[5.5]undecane, 1,6-dioxaspiro[4.5]decane, and 1,6-dioxaspiro[4.4]nonane types have been prepared from carbohydrates in pyranose or furanose forms. The spirocyclization reaction has been accomplished from a conveniently homologated carbohydrate by an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals. Thus, 2,3,4,6-tetra-O-benzyl-1-deoxy-1-(3'-hydroxypropyl)-alpha-D-glucopyranose (2) was photolyzed with visible light in the presence of (diacetoxyiodo)benzene and iodine to give a mixture of (1R)-(3) and (1S)-2,3,4,6-tetra-O-benzyl-1-deoxy-D-glucopyranose-1-spiro-2'-tetrahydrofuran (4). The photolysis of methyl 6-deoxy-6-(2'-hydroxyethyl)-2,3,4-tri-O-methyl-alpha-D-glucopyranoside (8) gave the isomeric spiroacetals methyl (5S)- (9) and (5R)-6-deoxy-5,2'-epoxy-6-ethyl-2,3,4-tri-O-methyl-alpha-D-glucopyranoside (10) in which the spirocenter is now located at C-5. The spiroacetals of the [5.5]undecane series: methyl (5R)- (19) and (5S)-6-deoxy-5,3'-epoxy-2,3,4-tri-O-methyl-6-propyl-beta-D-glucopyranoside (20) have been prepared starting from methyl 6-deoxy-6-(3'-hydroxypropyl)-2,3,4-tri-O-methyl-beta-D-glucopyranoside (18). The reaction has also been applied to hexofuranoses and 1-deoxy-1-(3'-hydroxypropyl)-2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose (21) gave rise to (1S)- (22) and (1R)-1-deoxy-2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2'-tetrahydrofuran (23); and 1-deoxy-1-(4'-hydroxybutyl)-2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose (28) to (1R)- (30) and (1S)-1-deoxy-2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2'-tetrahydropyran (32). Both spiroacetal enantiomers are formally available from the same carbohydrate.     

Organoselenium mediated asymmetric cyclizations. Synthesis of enantiomerically pure 1,6-dioxaspiro[4.4]nonanes

The asymmetric cyclization of 1-hydroxyoct-7-en-4-one, promoted by camphorselenenyl tetrafluoroborate, generated from camphor diselenide and silver tetrafluoroborate in dichloromethane at room temperature, afforded a mixture of two diastereoisomeric E- and two diastereoisomeric Z-2-[(camphorseleno)methyl]-1,6-dioxaspiro[4.4]nonanes. These were separated by medium pressure liquid chromatography and then deselenenylated with triphenyltin hydride and AIBN to give enantiomerically pure 2-methyl-1,6-dioxaspiro[4.4]nonanes. The camphorseleno group was also substituted by an allyl function using allyltributyltin in the presence of AIBN.     

Dioxolane-to-bridged acetal-to-spiroketal via ring-closing metathesis and rearrangement: a novel route to 1,7-dioxaspiro[5.5]undecanes

Several examples of 1,7-dioxaspiro[5.5]undecane spiroketal systems have been synthesized from the common bicyclic intermediate 1 via acid-catalyzed rearrangement. Intermolecular ketalization of C(2) symmetric diene diol 3 with ketone 9 and then desymmetrization by ring-closing metathesis rapidly constructs bicyclic acetal 1. The locked conformation and steric bias of 1 allow stereoselective functionalization of one or both double bonds before spiroketalization.     

Sex pheromone biosynthesis in the female olive fruit-fly. Double labelling from [18O2]-dioxygen into 1,7-dioxaspiro[5.5]undecane

The demonstration that both oxygen atoms of 1,7-dioxaspiro[5.5]undecane (1), the sex-pheromone of the female olive fly, originate from dioxygen, strongly implicates monooxygenase mediated processes in assembly of (1), and reveals unexpected complexity in the formation of its nine-carbon precursor.     

Synthesis of the enantiomers of 3-hydroxy-1,7-dioxaspiro[5.5]undecane, a minor component of the olive fly pheromone

(3$\text{R}$,6$\text{R}$)-(?)-3-Hydroxy-1,7-dioxaspiro[5.5]undecane 3a and its antipode were synthesized from ($\text{S}$)-malic acid.     

新型树形化合物1,3,5-三-[7-(7-甲基-2,2-二-(2,2-二羟甲基-3-羟基丙氧基羰基)-6,8-二氧杂螺[3.5]-壬基)]苯的合成

以丙酮和甲酸乙酯为原料, 在醇钠的作用下合成了1,3,5-三乙酰基苯(1). 1与二溴新戊二醇在酸的作用下发生缩酮化反应, 制成1,3,5-三-(1-甲基-2,6-二氧杂-4,4-二溴甲基环己基)苯(2). 2与5,5-二甲基-4,6-二氧杂-1,3-环己二酮在乙醇钠的作用下合成了1,3,5-三-[7-(7-甲基-2,2-二-乙氧羰基-6,8-二氧杂螺[3.5]-壬基)]苯(3). 将3在氯仿中与季戊四醇进行酯交换反应得到产物1,3,5-三-[7-(7-甲基-2,2-二-(2,2-二羟甲基-3-羟基丙氧基羰基)-6,8-二氧杂螺[3.5]-壬基)]苯(4). 收率为47.7%. 标题化合物及中间产物使用IR, ¹H NMR和MS或元素分析进行了表征.     

Electrophysiological Responses of Bactrocera kraussi (Hardy) (Tephritidae) to Rectal Gland Secretions and Headspace Volatiles Emitted by Conspecific Males and Females

Pheromones are biologically important in fruit fly mating systems, and also have potential applications as attractants or mating disrupters for pest management. Bactrocera kraussi (Hardy) (Diptera: Tephritidae) is a polyphagous pest fruit fly for which the chemical profile of rectal glands is available for males but not for females. There have been no studies of the volatile emissions of either sex or of electrophysiological responses to these compounds. The present study (i) establishes the chemical profiles of rectal gland contents and volatiles emitted by both sexes of B. kraussi by gas chromatography–mass spectrometry (GC–MS) and (ii) evaluates the detection of the identified compounds by gas chromatography–electroantennogram detection (GC–EAD) and –electropalpogram detection (GC–EPD). Sixteen compounds are identified in the rectal glands of male B. kraussi and 29 compounds are identified in the rectal glands of females. Of these compounds, 5 were detected in the headspace of males and 13 were detected in the headspace of females. GC–EPD assays recorded strong signals in both sexes against (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-ethyl-7-mehtyl-1,6-dioxaspiro[4.5]decane isomer 2, (E,Z)/(Z,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, and (Z,Z)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. Male antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-methyl-6-pentyl-3,4-dihydro-2H-pyran, 6-hexyl-2-methyl-3,4-dihydro-2H-pyran, 6-oxononan-1-ol, ethyl dodecanoate, ethyl tetradecanoate and ethyl (Z)-hexadec-9-enoate, whereas female antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane and 2-methyl-6-pentyl-3,4-dihydro-2H-pyran only. These compounds are candidates as pheromones mediating sexual interactions in B. kraussi.     

Reactions of 6,6-dialkyl-5,7-dioxo-4,8-dioxaspiro[2.5]octane-1,1,2,2-tetracarbonitriles with O-centered nucleophiles

The reactions of 6,6-dialkyl-5,7-dioxo-4,8-dioxaspiro[2.5]octane-1,1,2,2-tetracarbonitriles with primary aliphatic alcohols lead to the formation of alkyl 2,2,3,3-tetracyanocyclopropanecarboxylates; the reactions of the same compounds with ketone oximes give 2-amino-4,4-bis(alkylideneaminooxy)-6-(alkylidene-aminooxycarbonyl)-3-azabicyclo[3.1.0]hex-2-ene-1,5-dicarbonitriles, while with aldehyde oximes 2-amino-2-oxo-1,5-dicyano-3-azabicyclo[3.1.0]hex-2-ene-6-carboxylic acid is formed.     

Intramolecular michael addition reaction to chiral vinylic sulfoxides. An enantioselective synthesis of (R)- and (S)-1,7-dioxaspiro[5.5]undecane

(R)- and (S)-1,7-Dioxaspiro[5.5]undecane ((R)-1 and (S)-1), sex pheromone of an olive fly, was each stereoselectively synthesized using an intramolecular Michael addition of hydroxyl group to a chiral vinylic sulfoxide moiety as an asymmetric induction step.     

Syntheses of Racemic and Optically Active 4-Hydroxy-2-hydroxymethyl-1,7-dioxaspiro[5.5]undecanes

Racemic and optically active 4-hydroxy-2-hydroxymethyl-1,7-dioxaspiro[5.5]undecanes were prepared in six steps from butane-1,2,4-triol and valerolactone with the longest linear sequence being four steps.     

Synthetic studies of the HIV-1 protease inhibitive didemnaketals: stereocontrolled synthetic approach to the key mother spiroketals

The stereocontrolled synthesis of (2S,4R,6R,8S,10S,1'R,1' 'R)-2(acetylhydroxymethyl)-4,10-dimethyl-8(isopropenylhydroxymethyl)-1,7-dioxaspiro[5,5]undecane (4a) and its C1' '-epimer (4b), the key mother spiroketals of the HIV-1 protease inhibitive didemnaketals from the ascidian Didemnum sp., has been carried out through multisteps from the natural (R)-(+)-pulegone, which involved the diastereoselective construction of four chiral carbon centers(C-2, C-6, C-8, and C-1') by intramolecular chiral induce.     

Synthesis of the optically active forms of 4,10-dihydroxy-1,7-dioxaspiro[5.5]undecane and their conversion to the enantiomers of 1,7-dioxaspiro[5.5]undecane,the olive fly pheromone

Both the enantiomers of l,7-dioxaspiro[5.5]undecane, the major component of the pheromone of the olive fly (Dacus oleae), were synthesized from (S)-malic acid.     

Straightforward synthesis of 1,7-dioxaspiro[4.4]nonanes

The reaction of 2-chloromethyl-3-(2-methoxyethoxy)prop-1-ene with an excess of lithium powder and a catalytic amount of naphthalene (2.5%) in the presence of a carbonyl compound (E¹=R¹R²CO) in THF at −78 to 0 °C, followed by the addition of an epoxide [E²=R³R⁴C(O)CHR⁵] at 0 to 20 °C leads, after hydrolysis, to the expected methylidenic diols. These diols, in the presence of iodine and silver(I) oxide in dioxane-water, undergo double intramolecular iodoetherification to give the corresponding 1,7-dioxaspiro[4.4]nonanes, which in addition can be easily oxidised to a variety of 1,7-dioxaspiro[4.4]nonan-6-ones.     

Synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-thiaspiro[5.5]undecanes from exo-glycal

A new spirocyclization was developed for the synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-thiaspiro[5.5]undecanes by reaction of exo-glycal with aryl alcohols or thiophenols in the presence of Lewis acid BF₃·OEt₂. The reaction proceeded through tandem Ferrier rearrangement, glycosylation, and Friedel–Crafts alkylation to provide the corresponding products in good to excellent yields.     

Structure of the 1 : 1 Complex of Hexakis(2,3,6-tri- O-methyl) α-Cyclodextrin with ( R)-(-)-1,7-Dioxaspiro[5.5]undecane

The crystal structure of the 1 : 1 inclusion complex of hexakis(2,3,6-tri-O-methyl)- -cyclodextrin (TM CD) with 1,7-dioxaspiro[5.5]undecane (spiroacetal) is orthorhombic, space group C2221, with a = 24.002(2), b = 14.812(1), c = 21.792(2) Å V = 7747.3(11) Å3 and Z = 8. The molecular six-fold axis of TM CD coincides with the a two-fold crystallographic axis and the guest is located at the secondary methoxy group side, disordered over two positions related by that axis. The guest model used during the refinement is that of the (R)-enantiomer alone because trials to either refine a 1 : 1 mixture of (R)- and (S)-enantiomers or the (S)-enantiomer alone failed. The crystallographic evidence of enantioselectivity towards the (R)-enantiomer of spiroacetal was confirmed by independent experiments and may be attributed to numerous non bonding interactions between host and guest involving non conventional H-bonds.