General route to 4a-methylhydrofluorene diterpenoids: total syntheses of (+/-)-taiwaniaquinones d and h, (+/-)-taiwaniaquinol B, (+/-)-dichroanal B, and (+/-)-dichroanone

A general and convergent route for the synthesis of the 4a-methylhydrofluorene diterpenoids has been established through a common hexahydrofluorenone intermediate (10) obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane (13). The strategy has been successfully utilized for the synthesis of (+/-)-taiwaniaquinones D (3) and H (5), (+/-)-taiwaniaquinol B (1), (+/-)-dichroanal B (7), and (+/-)-dichroanone (8).     

Total synthesis of (+/-)-flustramines A and C, (+/-)-flustramide A, and (-)- and (+)-debromoflustramines A

Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.     

Total synthesis of (+/-)-pentacycloanammoxic acid

The first total synthesis of (+/-)-pentacycloanammoxic acid/methyl ester (1), an unusual naturally occurring fatty acid from Candidatus Brocadia anammoxidans, has been accomplished by the sequence of reactions shown in Scheme 1. The C20-structure of 1 was assembled with stereocontrol from three building blocks: cyclooctatetraene, 2-cyclopentenone, and 7-bromoheptanoic acid. The synthesis of 1 confirms the proposed structure of 1. The mode of biosynthesis and absolute configuration have yet to be clarified.     

Total synthesis of (+/-)-aspidospermidine

(+/-)-Aspidospermidine (1) has been synthesized from readily available methyl 3-ethyl-2-oxocylo-pentanecarboxylate (17) in 5.9% yield over 13 steps. The key step of the synthesis is an intramolecular cascade reaction that simultaneously forms the B, C, and D rings of 1. A high-yielding method of closing the remaining E ring is also described.     

Efficient synthesis of fused bicyclic glutarimides. Its application to (+/-)-alloyohimbane and louisianin D

[reaction: see text] The reaction of alpha-sulfonyl acetamide 1 with various cyclic unsaturated esters 2 to fused bicyclic glutarimides is reported. Syntheses of (+/-)-alloyohimbane (4) and louisianin D (5) have been accomplished.     

Total synthesis of (+/-)-2-isocyanoallopupukeanane

2-Isocyanoallopupukeanane (4) has been obtained in racemic form from methyl 2-exo-methylbicyclo[2.2.1]hept-5-ene-2-endo-carboxylate via dibromocarbene addition, S(N)2' displacement, chain extension, and elaboration of the unsaturated ketone 12c which underwent an intramolecular hetero-Diels-Alder reaction to afford 13 containing all the skeletal carbon atoms. The dihydropyran unit was cleaved by ozonolysis to give the tricarbocyclic intermediate which required seven more steps to complete the synthesis.     

A series of lanthanide-transition metal frameworks based on 1-, 2-, and 3D metal-organic motifs linked by different 1D copper(I) halide motifs

Hydrothermal reactions of lanthanide(III) oxide and copper halide with isonicotinic acid (Hina) and pyridine-2,3-dicarboxylic acid (H2pdc) or 1,2-benzenedicarboxylic acid (H2bdc) lead to three novel lanthanide(III)-copper(I) heterometallic compounds, namely, [Ce2(ina)5(na)2(H2O)2][Cu5Br4] (1, na=nicotinic acid), [Er4(ina)8(bdc)2(OH)(H2O)5][Cu8I7] (2), and [Ce3(ina)8(bdc)(H2O)4][Cu7Br6] (3). Compound 1 is constructed from two distinct units of the Ln-organic double chains and inorganic [Cu5Br4]nn+ chains. Compound 2 consists of 2D Ln-organic layers and 1D [Cu8I7]nn+ cluster chains. Compound 3 can be viewed as a 1D [Cu6Br6]n chainlike motif inserted into the channels of a 3D Ln-Cu-organic motif. Compounds 1-3 exhibit three different 1D inorganic copper(I)-halide chains interconnected with metal-organic 1D chains, 2D layers, and 3D nets resulting in three mixed-motif non-interpenetrating heterometallic Cu-halide-lanthanide (Ln)-organic frameworks, which represent good examples and a facile method to construct such mixed-motif heterometallic compounds. Furthermore, the IR, TGA, and UV-vis spectra of 1-3 were also studied.     

C-H insertion approach to the synthesis of endo,exo-furofuranones: synthesis of (+/-)-asarinin, (+/-)-epimagnolin A, and (+/-)-fargesin

A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.     

Total synthesis of (+/-)-alpha-isosparteine, (+/-)-beta-isosparteine, and (+/-)-sparteine from a common tetraoxobispidine intermediate

The three title alkaloids were separately prepared in stereocontrolled fashion from a common tetraoxobispidine precursor, 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (16). Bisimide 16 was generated from malonate via acid promoted cyclization of the Knoevenagel condensation adduct 1,1,3,3-propanetetracarboxamide. (+/-)-alpha-Isosparteine (dl-2) was elaborated from 16 in 28% overall yield by a two-directional synthetic sequence composed of four reactions: double addition of allylmagnesium bromide, ring-closing olefin metathesis (RCM), hydrogenation, and borane mediated reduction. (+/-)-beta-Isosparteine (dl-3) was targeted along similar lines by a strategic reversal in allylation and reduction operations on the core synthon. Thus, 16 was advanced to dl-3 in five steps and 12% overall yield by a reaction sequence commencing with sodium borohydride mediated reduction and followed by double Sakurai-type allylation of the resulting bishemiaminal. The synthesis of dl-3 was concluded by RCM and then global reduction (H2, Pd/C; LiAlH4). The final target, (+/-)-sparteine (dl-1), was secured in six steps and 11% overall yield from 16 by monoreduction and Sakurai allylation, followed by allyl Grignard addition and then RCM and global reduction as before. Reasons for the inherent C2-type regioselectivity of net double nucleophilic additions to tetraoxobispidines are discussed and enantioselective oxazaborolidine mediated reduction of the N,N'-dibenzyl congener of 16 is reported.     

Formal syntheses of (+/-)-pinnaic acid and (+/-)-halichlorine

[chemical reaction: see text]. Concise formal syntheses of marine alkaloids (+/-)-pinnaic acid (1) and (+/-)-halichlorine (2) have been accomplished from a common intermediate. The syntheses illustrate the utility of selective olefin cross metathesis methodologies for the elaboration of advanced synthetic intermediates in complex molecule synthesis.     

Expeditious syntheses of (+/-)-5-oxosilphiperfol-6-ene and (+/-)-silphiperfol-6-ene

[reaction: see text]Stereocontrolled syntheses of 5-oxosilphiperfol-6-ene (1) and silphiperfol-6-ene (2) have been accomplished in four and five steps, with overall yields of 32% and 26%, respectively, from 1-acetyl-3-methylcylopentene. The strategy features two pivotal reactions: (a) a Diels-Alder reaction between 1,3-dimethylcyclopentadiene and 1-acetyl-3-methylcyclopentene, which proceeds with remarkable regio-, endo-, and diastereofacial selectivities, and (b) an intramolecular Paterno-Büchi reaction to snap together the triquinane framework.     

Total synthesis of (+/-)-scopadulin.

The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.     

First total synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone

[reaction: see text] A simple synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone has been achieved through a common hexahydrofluorenone intermediate obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane.     

Synthesis and Crystal Structure of a Novel 1D Magnesium(II) Coordination Polymer Constructed by L-Cysteic Acid

A novel coordination polymer [Mg(L)(H2O)2]·H2O] (LH2 = L-cysteic acid) has been synthesized and characterized by elemental analysis, IR and single-crystal X-ray diffraction. The crystal crystallizes in orthorhombic system, space group P212121, with a = 5.962(3), b = 11.224(6), c = 13.664(7) , V = 914.3(8) 3, Z = 4, Mr = 245.50, Dc = 1.783 g/cm3, μ = 0.445 mm–1, flack parameter = 0.32(16), F(000) = 512, the final R = 0.0458 and wR = 0.1172 for 1578 observed reflections with I > 2σ(I). The Mg(II) atom shows an octahedral geometry defined by two carboxyl O atoms from two different L-cysteic acid ligands, one carboxyl O atom and one amino N atom from the adjacent ligand, and two aqua ligands. The Mg(II) atoms are bridged by L-cysteic acid ligands, leading to a 1D infinite zigzag chain. In the structure there are extensive hydrogen bonds, through which the complex completes its 3D framework structure.     

Synthesis and Crystal Structure of a Novel 1D Magnesium (Ⅱ) Coordination Polymer Constructed by L-Cysteic Acid

A novel coordination polymer [Mg(L)(H2O)2]·H2O] (LH2=L-cysteic acid) has been synthesized and characterized by elemental analysis, IR and single-crystal X-ray diffraction.The crystal crystallizes in orthorhombic system, space group P212121, with a=5.962(3), b=11.224(6), c=13.664(7)(A), V=914.3(8) (A)3, Z=4, Mr=245.50, Dc=1.783 g/cm3,μ=0.445 mm-1,flack parameter=0.32(16), F(000)=512, the final R=0.0458 and wR=0.1172 for 1578 observed reflections with I ＞ 2σ(Ⅰ). The Mg(Ⅱ) atom shows an octahedral geometry defined by two carboxyl O atoms from two different L-cysteic acid ligands, one carboxyl O atom and one amino N atom from the adjacent ligand, and two aqua ligands. The Mg(Ⅱ) atoms are bridged by L-cysteic acid ligands, leading to a 1D infinite zigzag chain. In the structure there are extensive hydrogen bonds,through which the complex completes its 3D framework structure.     

1D helix, 2D brick-wall and herringbone, and 3D interpenetration d10 metal-organic framework structures assembled from pyridine-2,6-dicarboxylic acid N-oxide

Five novel interesting d(10) metal coordination polymers, [Zn(PDCO)(H2O)2]n (PDCO = pyridine-2,6-dicarboxylic acid N-oxide) (1), [Zn2(PDCO)2(4,4'-bpy)2(H2O)2.3H2O]n (bpy = bipyridine) (2), [Zn(PDCO)(bix)]n (bix = 1,4-bis(imidazol-1-ylmethyl)benzene) (3), [Zn(PDCO)(bbi).0.5H2O]n (bbi = 1,1'-(1,4-butanediyl)bis(imidazole)) (4), and [Cd(PDCO)(bix)(1.5).1.5H2O]n (5), have been synthesized under hydrothermal conditions and structurally characterized. Polymer 1 possesses a one-dimensional (1D) helical chainlike structure with 4(1) helices running along the c-axis with a pitch of 10.090 Angstroms. Polymer 2 has an infinite chiral two-dimensional (2D) brick-wall-like layer structure in the ac plane built from achiral components, while both 3 and 4 exhibit an infinite 2D herringbone architecture, respectively extended in the ac and ab plane. Polymer 5 features a most remarkable and unique three-dimensional (3D) porous framework with 2-fold interpenetration related by symmetry, which contains channels in the b and c directions, both distributed in a rectangular grid fashion. Compounds 1-5, with systematic variation in dimensionality from 1D to 2D to 3D, are the first examples of d(10) metal coordination polymers into which pyridinedicarboxylic acid N-oxide has been introduced. In addition, polymers 1, 4, and 5 display strong blue fluorescent emissions in the solid state. Polymer 3 exhibits a strong SHG response, estimated to be approximately 0.9 times that of urea.     

Synthesis of (+/-)-phloeodictine A1

The antitumor antibiotic phloeodictine A1 (2) has been synthesized by a convergent seven-step route in 8% overall yield. The key step was the Eguchi aza-Wittig reaction of 6 to give 13 followed by a retro Diels-Alder reaction to liberate 5. Addition of 11-dodecenylmagnesium bromide to 5 to give 4b, alkylation with 18b, and deprotection completed the first synthesis of 2.     

Synthetic studies on the cornexistins: synthesis of (+/-)-5-epi-hydroxycornexistin

The synthesis of 5-epi-hydroxycornexistin (44), a diastereoisomer of the herbicidal natural product hydroxycornexistin (2) has been completed. Palladium mediated sp(2)-sp(3) coupling of the stannane 25 and the chloride 31 and ring-closing metathesis of the resulting diene 32 has been used to construct the tricyclic lactone 34a, which possesses the nine-membered carbocyclic core found in the natural product, in good yield. The synthesis of 5-epi-hydroxycornexistin (44) has established the feasibility of using a furan as precursor for the cyclic anhydride unit present in the natural product and has demonstrated the viability of other late-stage transformations that will be used to prepare hydroxycornexistin (2).     

Structural evolution and magnetic properties of Co(II) coordination polymers varied from 1D to 3D constructed by 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene

Seven Co(II) coordination polymers, [Co(btx)(3)(H(2)O)(2)](ClO(4))(2)·(btx)·2H(2)O (1), [Co(btx)(3)(H(2)O)(2)](BF(4))(2)·(btx)·2H(2)O (2), [Co(btx)(2)(H(2)O)(2)](NO(3))(2)·2H(2)O (3), [Co(btx)(2)Cl(2)] (4), [Co(btx)(BA)(2)(H(2)O)(2)]·2HBA (5), [Co(btx)(IPA)] (6) and [Co(3)(btx)(3)(BTA)(2)(H(2)O)(2)] (7) (btx = (1,4-bis(1,2,4-triazol-1-ylmethyl)benzene), HBA = benzoic acid, H(2)IPA = isophthalic acid, H(3)BTA = benzene-1,3,5-tricarboxylic acid), have been hydrothermally synthesized and characterized. 1 and 2 are isostructural and show a 1D Co-μ(2)-btx-Co chain structure, in which btx acts as both a bridging and terminal ligand. 3 is also a 1D chain structure but different from 1 and 2. The Co(II) ions are bridged by double μ(2)-btx to form Co(2)-btx(2) rings, which were further connected into 1D chains by sharing the Co(II) ions of the rings. 4 exists as a 2D grid with (4,4) topology structure. When aromatic acid was introduced to the synthetic system, three other coordination polymers 5-7 were obtained. In 5, the 1D chain is as that of 1, except that the terminal ligand was replaced by BA(-). 6 shows a two-fold parallel interpenetration framework featuring a 6-c uninodal net with (3(3),4(6),5(5),6) Schlafli topological symbol. 7 is an interesting 3D framework, which contains a 2-nodal net motif with the unprecedented (3(6),4(2),5(6),6)(3(9),4(9),5(3))(2) topology structure. The influence of the varieties of the structures and magnetic properties are studied and discussed in detail.     

Total synthesis of (+/-)-symbioimine

The synthesis of (+/-)-symbioimine (1) has been completed in only 12 linear steps in 8% overall yield. The key step is the treatment of 13b with BF3.Et2O to generate N-carboalkoxydihydropyridinium cation 14b, which undergoes a novel stereospecific intramolecular Diels-Alder reaction to give adduct 16b in 42% yield. Cleavage of the N-Troc group of 16b afforded imine 24b stereospecifically. Cleavage of the TBDMS ethers and sulfation provided (+/-)-symbioimine (1). [reaction: see text].