Guanidinium phenylarsonate-guanidine-water (1/1/2)

In the structure of CH6N3+ C6H6AsO3- . CH5N3 . 2H2O, the phenylarsonate anion gives two R2/2(8) cyclic hydrogen-bonding interactions, one with a guanidinium cation, the other with a guanidine molecule. The anions are also bridged by the water molecules, one of which completes a cyclic R3/5(9) hydrogen-bonding association with the guanidinum cation, conjoint with one of the three R^2^~2~(8) associations about that ion, as well as forming an R1/2(6) cyclic association with the guanidine molecule. The result is a three-dimensional framework structure.

Synthesis, Reactivity, Structural Aspects, and Solution Dynamics of Cyclopalladated Compounds of N,N `,N `'-Tris(2-anisyl)guanidine

N,N',N `'-Tris(2-anisyl)guanidine, (ArNH)(2)C=NAr (Ar = 2-(MeO)C6H4), was cyclopallaclated with Pd(OC(O)R)(2) (R = Me, CF3) in toluene at 70 degrees C to afford palladacycles Pd{kappa(2)(C,N)-C6H3-(OMe)-3(NHC(NHAr)(=NAr))-2}(mu-OC(O)R)](2)(R = Me (1a) and CF3 (1b)) in 87% and 95% yield, respectively. Palladacycle 1a was subjected to a metathetical reaction with LiBr in aqueous ethanol at 78 degrees C to afford palladacycle Pd{kappa(2)(C,N)-C6H3(OMe)-3(NHC(NHAr)(=NAr))-2}(mu-Br)](2) (2) in 90% yield. Palladacycle 2 was subjected to a bridge-splitting reaction with Lewis bases in CH2Cl2 to afford the monomeric palladacycles Pd{kappa(2)(C,N)-C6H3(OMe)-3(NHC(NHAr)(=NAr))-2}Br(L)] (L = 2,6-Me2C5H3N (3a), 2,4-Me2C5H3N (3b), 3,5-Me2C5H3N (3c), XyNC (Xy = 2,6-Me2C6H3; 4a), (BuNC)-Bu-t (4b), and PPh3 (5)) in 87-95% yield. Palladacycle 2 upon reaction with 2 equiv of XyNC in CH2Cl2 afforded an unanticipated palladacycle, Pd{kappa(2)(C,N)-C(=NXy)(C6H3(OMe)-4)-2(N=C-(NH Ar)(2))-3} Br(CNXy)] (6) in 93% yield, and the driving force for the formation of 6 was ascribed to a ring contraction followed by amine-imine tautomerization. Palladacycles 1 a,b revealed a dimeric transoid in-in conformation with ``open book'' framework in the solid state. In solution, 1 a exhibited a fluxional behavior ascribed to the six-membered ``(C,N)Pd'' ring inversion and partly dissociates to the pincer type and kappa(2)-O,O'-OAc monomeric palladacycles by an anchimerically assisted acetate cleavage process as studied by variable-temperature H-1 NMR data. Palladacycles 3a,b revealed a unique trans configuration around the palladium with lutidine being placed trans to the Pd-C bond, whereas cis stereochemistry was observed between the Pd-C bond and the Lewis base in 4a (as determined by X-ray diffraction data) and 5 (as determined by P-31 and C-13 NMR data). The aforementioned stereochemical difference was explained by invoking relative hardness/softness of the donor atoms around the palladium center. In solution, palladacycles 3a-c exist as a mixture of two interconverting boat conformers via a planar intermediate without any bond breaking due to the six-membered ``(C,N)Pd'' ring inversion, whereas palladacycles 4a,b and 5 exist as a single isomer, as deduced from detailed H-1 NMR studies.

Guanidine catalyzed aerobic reduction: a selective aerobic hydrogenation of olefins using aqueous hydrazine

An efficient aerobic reduction of olefins, internal as well as terminal, is developed using guanidine as an organocatalyst. A remarkable chemoselectivity in reduction has been demonstrated in the presence of a variety of functional groups and protective groups and a selective reduction of a terminal olefin in the presence of an internal olefin is revealed.

Depalladation of Neutral Monoalkyne- and Dialkyne-Inserted Palladacycles and Alkyne Insertion/Depalladation Reactions of Cationic Palladacycles Derived from N,N `,N `'-Triarylguanidines as Facile Routes for Guanidine-Containing Heterocycles/Carbocycles: Synthetic, Structural, and Mechanistic Aspects

Depalladation of the monoalkyne-inserted cyclopalldated guanidines (kappa 2(C,N)Pd(2,6-Me2C5H3N)Br] (I and II) in PhCl under reflux conditions and that of the dialkyne-inserted cyclopalladated guanidine kappa(2)(C,N):eta(2)(C=C)PdBr] (III) in pyridine under reflux conditions afforded a guanidine-containing indole (1), imidaziondole (2), and benzazepine (3) in 80%, 67%, and 76%, yields, respectively. trans-L2PdBr2] species (L = 2,6-Me2C5H3N, C5H5N) were also isolated in the aforementioned reactions in 35%, 42%, and 40% yields. Further , the reaction of the cyclopalladated guanidine kappa(2)(C,N)Pd(mu-Br)](2) (IV) with AgBF4 in a CH2Cl2/MeCN mixture afforded the cationic pincer type cyclopalladated guanidine kappa(3)(C,N,O)Pd(MeCN)]BF4] (4) in 85% yield and this palladacycle upon crystallization in MeCN and the reaction of kappa(2)(C,N)Pd(mu-Br)](2) (V) with AgBf(4) in a CH2Cl2/MeCN mixture afforded the cationic palladacycles {kappa(2)(C,N)Pd(MeCN)(2)]BF4](5 and 6) in 89% and 91% yields, respectively. The separate reactions of 4 with 2 equiv of methyl phenylpropiolate (MPP) or diphenylacetylene (DPA) and the reaction of 5 with 2 equiv of MPP in PhCl at 110 degrees C afforded the guanidine-containing quinazolinium tetrafluoroborate 7 in 25-32% yields. The reaction of 6 with 2 equiv of DPA under otherwise identical conditions afforded the unsymmetrically substituted guanidinium tetrafluoroborate 8, containing a highly substituted naphthalene unit, in 82% yield. Compounds 1-8 were characterized by analytical and spectroscopic techniques, and all compounds except 4 were characterized by single-crystal X-ray diffraction. The Molecular structure of 2 and 3 are nove, as the framework in the former arises due to the formation of two C-N bonds upon depalladation while the butadienyl unit in the latter revealed cis,cis stereochemistry, a-feature unprecedented in alkyne insertion chemistry. Plausible pathways for the formation of heterocycles/carbocycles are proposed. the influence of substitutents on the aryl rings fo the cyclopalladated guanidine moiety and those on alkynes upon the nature of the products in addressed. Heterocycles 1 and 7 revealed the presence of two rotamers in about a 1.00:0.43 ratio in CDCl3 and in about a 1.00:0.14 ratio in CD3OD, respectively, as detected by H-1 NMR spectroscopy while in CD3CN and DMSO-d(6) (1) and CD3CN and CDCl3 (7), these heterocycles revealed the presence of a single rotamer. These spectral features are attributed to the restricted C-N single-bond rotation of the CN3 unit of the guanidine moiety, which possibly arises from steric constraint due to the formation of a N-H center dot center dot center dot Cl hydrogen bond with CDCl3 (1) and N-H center dot center dot center dot O and O-D center dot center dot center dot O hydrogen bonds with CD3OD (7).

Guanidine/Pd(OAc)(2)-catalyzed room temperature Suzuki cross-coupling reaction in aqueous media under aerobic conditions

A highly efficient Pd(OAc)(2)/guanidine aqueous system for the room temperature Suzuki cross-coupling reaction has been developed. The new water-soluble and air-stable catalyst Pd(OAc)(2)(.)(1f)(2) from Pd(OAc)(2) and 1,1,3,3-tetramethyl-2-n-butylguanidine (1f) was synthesized and characterized by X-ray crystallography. In the presence of Pd(OAc)(2)(.)(1f)(2), coupling of arylboronic acids with a wide range of aryl halides, including aryl iodides, aryl bromides, even activated aryl chlorides, was carried out smoothly in aqueous solvent to afford the cross-coupling products in good to excellent yields and high turnover numbers (TONs) (TONs up to 850 000 for the reaction of 1-iodo-4-nitrobenzene and phenylboronic acid). Furthermore, this mild protocol could tolerate a broad range of functional groups.

Bronsted guanidine acid-base ionic liquids: Novel reaction media for the palladium-catalyzed Heck reaction

Bronsted acid-base ionic liquids (GILs) based on guanidine and acetic acid are efficient reaction media for palladium-catalyzed Heck reactions. They offer the advantages of high activity and reusability. GIL2 plays multiple roles in the reaction: it could act as solvent, as a strong base to facilitate beta-hydride elimination, and as a ligand to stabilize activated Pd species.

A New Stereocontrolled Total Synthesis of the Mast Cell inhibitory Alkaloid, (+)-Monanchorin, via the Wittig Reaction of a Stabilized Ylide with a Cyclic Guanidine Hemiaminal

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An asymmetric total synthesis of the mast cell inhibitor (+)-monanchorin is reported in which a Sharpless AD on 11 and a cyclic sulfate ring opening with an azide feature as key steps. After further manipulation, a novel guanidine-controlled ester reduction provided the guanidine-hemiaminal 25 which underwent Wittig olefination to give 27. Hydrogenation and a second guanidine-controlled reduction of the ester in 28, to obtain aldehyde 29, then set up a trifluoroacetic acid mediated cyclization to give (+)-monanchorin TFA salt.

Synthesis and utilization of guanidine catalysts for applications directed towards the preparation of butenolide and modified amino acid derivatives

Development of guanidine catalysts is explored through direct iminium chloride and amine coupling, alongside a 2-chloro-l,3-dimethyl-IH-imidazol-:-3-ium chloride (DMC) induced thiourea cyclization. Synthesized achiral catalyst N-(5Hdibenzo[ d,t][1,3]diazepin-6(7H)-ylidene)-3,5-bis(trifluoromethyl) aniline proved unsuccessful towards O-acyl migrations, however successfully catalyzed the vinylogous aldol reaction between dicbloro furanone and benzaldehyde. Incorporating chirality into the guanidine catalyst utilizing a (R)-phenylalaninol auxiliary, generating (R)-2-((5Hdibenzo[ d,t] [1,3 ]diazepin-6(7H)-ylidene ) amino )-3 -phenylpropan-l-ol, demonstrated enantioselectivity for a variety of adducts. Highest enantiomeric excess (ee) was afforded between dibromofuranone and p-chlorobenzaldehyde, affording the syn conformation in 96% ee and the anti in 54% ee, with an overall yield of30%. Attempts to increase asymmetric induction were focused on incorporation of axial chirality to the (R)phenylalaninol catalyst using binaphthyl diamine. Incorporation of (S)-binaphthyl exhibited destructive selectivity, whereas incorporation of (R)-binaphthyl demonstrated no effects on enantioselectivity. Current studies are being directed towards identifying the catalytic properties of asymmetric induction with further studies are being aimed towards increasing enantioselectivity by increasing backbone steric bulk.

Synthesis of a 7-Membered Biaryl Guanidine Catalyst and its Use in the Vinylogous Aldol Reaction

The present thesis outlines the preparation of a 7-membered guanidine. Initial efforts to obtain this guanidine via 2-chloro-1,3-dimethylimidazolinium chloride induced ring forming chemistry failed to provide the target in a reproducible fashion. Changing strategies, we were able to obtain the desired guanidine through CuCl mediated amination of a 7-membered thiourea intermediate to arrive at the target. In addition, the catalytic activity of this compound was evaluated in a vinylogous aldol reaction of dibromofuranone and four aromatic aldehydes to generate chiral γ-butenolides with modest to good enantiomeric excess. It was found that electron-poor aldehydes resulted in higher, 81% ee, whereas electron rich aldehydes led to low, 41% ee, levels of enantiomeric excess.

Antisense-induced myostatin exon skipping leads to muscle hypertrophy in mice following Octa‑guanidine morpholino oligomer treatment

Myostatin is a negative regulator of muscle mass, and several strategies are being developed to knockdown its expression to improve muscle-wasting conditions. Strategies using antimyostatin-blocking antibodies, inhibitory-binding partners, signal transduction blockers, and RNA interference system (RNAi)-based knockdown have yielded promising results and increased muscle mass in experimental animals. These approaches have, however, a number of disadvantages such as transient effects or adverse immune complications. We report here the use of antisense oligonucleotides (AOs) to manipulate myostatin pre-mRNA splicing and knockdown myostatin expression. Both 2’O-methyl phosphorothioate RNA (2’OMePS) and phosphorodiamidate morpholino oligomers (PMO) led to efficient exon skipping in vitro and in vivo and knockdown of myostatin at the transcript level. The substantial myostatin exon skipping observed after systemic injection of Vivo-PMO into normal mice led to a significant increase in soleus muscle mass as compared to the controls injected with normal saline suggesting that this approach could be feasible to ameliorate muscle-wasting pathologies.

Facile synthesis of guanidine functionalised building blocks

Three useful developments in the preparation of guanidines are presented herein. A collection of bis(Boc)aminoalkylguanidines (n=2, 3, 4 and 6; Boc=tert-butoxycarbonyl), known to be prone to cyclisation, have been synthesised and isolated without chromatography as shelf-stable sulfonate salts in good yield (up to 94%). Secondly, a selection of guanidines tethered to a range of other functional groups, including alkyne, alkene, alcohol, and azide, have been prepared in good yields with no requirement for a purification step, and thirdly an inexpensive, high-yielding (93%), and facile synthesis of N,N'-bis(Boc)guanidine, a key precursor for N,N'-bis(Boc)-N'-triflylguanidine, is described in which the need for chromatographic purification is again obviated.

Cytotoxic Guanidine Alkaloids from Pterogyne nitens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)