Octane Fragment Research Articles

The Total Synthesis of Mollanol A by a Convergent Strategy

AbstractHere, we briefly highlight our 15-step total synthesis of mollanol A, the first isolated member of the mollane-type grayanoids, which relied on a convergent strategy. A Stille coupling and a vinylogous aldol reaction/intramolecular oxa-Michael addition sequence were used to assemble the two fragments that featured most of the important chiral centers and nearly all the essential oxidation states of the natural product. The bicyclo[3.2.1]octane fragment was synthesized by using an InCl3-catalyzed Conia–ene cyclization reaction. The challenging tetrasubstituted alkene was constructed through a 1,4-reduction of the conjugated alkenes at a late stage.1 Introduction2 Total Synthesis of Mollanol A3 Conclusion

New phosphorus-containing polycycles with a spiroamine group

Aim. To synthesize hexahydrospiro[cyclopropane-1,10’-pyrido[1,2-c]quinazoline] and 2-λ5-benzo[f][1,4,2]diazaphosphepine derivatives – new N-P containing heterocyclic compounds with the 6-azaspiro[2.5]octane fragment.Results and discussion. A new analog of the powerful electrophilic reagent – “Alder dimer” ‒ was obtained from the interaction of triflic anhydride and spiro(4-cyclopropane) piperidinyl formamide, and further used to synthesize new Nʹ-PV- and PIII-substituted Νʹ-phenyl, Νʹʹ-hexahydro(azaspiro)octylformamidinium salts – precursors of acyclic N-phosphorylated diamino carbenes with a spiroamine group. It has been shown that acyclic N-phosphorylated diaminocarbenes are transient species affording various products. The structure of the final product is primarily determined by nature of the phosphorus-bearing substituent, namely a phosphoryl or phosphino-group. N-PV-substituted carbene undergoes a 1,2-phosphorus shift with the formation of (selenophosphoryl)formamidine in a high yield. For N-PIII-substituted carbene a compatible 1,3-H shift also occurs with the formation of an intermediate azomethine ylide converted into a new heterocyclic system – hexahydrospirocyclopropane -1,10’-pyrido[1,2-c]quinazoline. Under the action of acid an unexpected further expansion of the 6-member ring occurs with the formation of a diazepine derivative.Experimental part. The reaction of Alder reagent with N-PV-seleno phosphoryl arylamides afforded N-phosphorus substituted formamidinium salts, which are easily reduced to PIII analogues. In addition to the corresponding formamidines, the new N-phosphorylated spiroamine-containing polycyclic system was isolated from the reaction mixture formed by the deprotonation of such salts with a strong non-nucleophilic base.Conclusions. The Alder reagent approach allows synthesizing precursors of acyclic formamidine carbenes with the spiroamine group. Such carbenes are unstable. By converting these compounds N-PIII-substituted tetrahydropyrimidine and diazaphosphepine derivatives with the 6-azaspiro[2.5]octane fragment have been obtained for the first time.

Synthetic efforts toward the bicyclo[3.2.1]octane fragment of rhodojaponin III

Rhodojaponin III is a grayanane-type diterpenoid natural product with a novel chemical scaffold. It shows potent antinociceptive activity and may represent a new class of natural non-opioid analgesics with a novel mode of action. We explored the Au(I)-catalyzed Conia-ene cyclization and the Mn(III)-mediated radical cyclization of alkynyl ketones for the synthesis of the bicyclo[3.2.1]octane fragment of rhodojaponin III. These strategies will be applicable in the synthesis of rhodojaponin III and analogs for future biological studies.

Convergent Total Synthesis of Principinol D, a Rearranged Kaurane Diterpenoid.

The total synthesis of principinol D, a rearranged kaurane diterpenoid, is reported. This grayanane natural product is constructed via a convergent fragment coupling approach, wherein the central seven-membered ring is synthesized at a late stage. The bicyclo[3.2.1]octane fragment is accessed by a Ni-catalyzed α-vinylation reaction. Strategic reductions include a diastereoselective SmI2-mediated ketone reduction with PhSH and a new protocol for selective ester reduction in the presence of ketones. The convergent strategy reported herein may be an entry point to the larger class of kaurane diterpenoids.

ChemInform Abstract: Synthesis of New Oxabicyclo[3.3.0]octane Nucleoside Analogues with Pyrimidine Bases.

AbstractThe synthesis of new isomeric nucleosides (III) and (IV) with an oxabicyclo[3.3.0]octane fragment in the sugar moiety is performed by Vorbruggen glycosylation.

1,2-Dimethyl-1,4-diazoniabicyclo[2.2.2]octane tetrachloridocuprate(II)

In the title compound, (C8H18N2)[CuCl4], torsion angles on the ethyl­ene bridges of the 1,4-diazo­niabicyclo­[2.2.2]octane fragment are in the range 11.9 (5)–15.0 (5)° and the [CuCl4]2− anion has a strongly distorted tetra­hedral geometry. The cation is connected to the anion via three-center N—H⋯Cl hydrogen bonds.

Synthesis of RO5114436

RO5114436 is a chemokine receptor CCR5 antagonist that is a lead for the treatment of HIV and inflammatory disorders. The ­thirteen-step synthesis depicted features (1) a ­ruthenium-catalyzed asymmetric hydrogenation of an unprotected enamino ester using the (R)-MeOBIPHEP ligand and (2) a large-scale dipolar cycloaddition to generate the 3,7-diazabicyclo-[3.3.0]octane fragment H.

On the Structure of Palau'amine: Evidence for the Revised Relative Configuration from Chemical Synthesis

Hexacyclic congeners 3 and 4 of palau'amine, which incorporate both guanidine functional groups and have the cis configuration of the azabicyclo[3.3.0]octane core, are prepared in 14 steps from cycloadduct 6. Synthetic access to these analogues allows the first direct comparison of NMR data for hexacyclic diguanidine structures having the originally proposed cis-azabicyclo[3.3.0]octane fragment with data for natural alkaloids of the palau'amine family. This comparison provides convincing evidence in favor of the recently proposed structural revision of these marine alkaloids, fully supporting the trans configuration of the central azabicyclo[3.3.0]octane ring system of palau'amine and congeners.

Synthesis of Molecular Motors Incorporating para‐Phenylene‐Conjugated or Bicyclo[2.2.2]octane‐Insulated Electroactive Groups

The insulating role of the bicyclo[2.2.2]octane fragment has been theoretically evaluated by comparing the electronic coupling parameter (V(ab)) in 1,4-bis(ferrocenyl)benzene (1) and 1,4-bis(ferrocenyl)bicyclo[2.2.2]octane (2). The geometries were optimized by DFT and an extended Hückel calculation was performed to evaluate V(ab) by the dimer splitting method. The calculations showed a 12-fold decrease of the electronic coupling from 60 meV for 1 to 5 meV for 2. The second part describes the synthesis of two potential molecular motors with one incorporating the insulating bicyclo[2.2.2]octane fragment. These molecules are based on a ruthenium complex bearing a tripodal stator functionalized to be anchored onto surfaces. The ferrocenyl electroactive groups and the cyclopentadienyl (Cp) rotor are connected through a p-phenylene spacer (5) or through a spacer incorporating an insulating bicyclo[2.2.2]octane moiety (6).

Synthesis of scopine 3-amino-2-phenylpropionate derivatives

The 8 azabicyclo[3.2.1]octane (tropane) fragment is found in some natural alkaloids (atropine, scopolamine, anatoxin, etc.).1—4 Like many other synthetic deriva tives of this heterocycle, they exhibit analgetic, hypoten sive, anti Parkinsonian, and methacholinolytic activities and are used in medical practice as chemotherapeutic drugs.5—10 In the present work, we developed a new method for the synthesis of scopine containing β amino acid deriva tives that may be of interest as physiologically active com pounds. The starting materials were scopolamine hydro bromide (1) and secondary amines such as diethyl amine (2a), piperidine (2b), and morpholine (2c). Heating of scopolamine hydrobromide 1 with diethyl amine 2a in the molar ratio 1 : 3 at 120 °C gave scopine 3 (N,N diethylamino) 2 phenylpropionate (3a) in ~10% yield. Reactions of scopolamine hydrobromide 1 with piperidine 2b and morpholine 2c were much more efficient: the yields of amino esters 3b and 3c were 88 and 70%, respectively. In all cases, racemization of the chiral center in the acid moiety of scopolamine took place. Under these conditions, the epoxide ring of scopolamine did not undergo opening in the presence of the aforemen tioned amines. In contrast to amines 2a—c, the reaction of L proline (2d) with scopolamine hydrobromide oc curred as esterification to give optically active scopine 2 phenyl 3 (pyrrolidin 2 ylcarbonyloxy)propionate (4) in 95% yield. When an aqueous solution of amine 2a or scopol amine rather than its hydrobromide 1 were used, the ester bond of scopolamine underwent very rapid hydrolysis to give scopoline (6 methyl 2 oxa 6 azatricyclo[3.3.1.03,7] nonan 4 ol) and tropic (3 hydroxy 2 phenylpropionic) acid.11 Interestingly, the reaction with isopropylamine yielded a complex mixture of products. Apparently, the formation of β amino acid esters 3a—c passes through the formation of scopine 2 phenylprop 2 enoate followed by the Michael addition of amines 2a—c to the activated C=C bond,12—14 which is evident from racemization of the optically active (–) S center of the acid fragment in scopolamine. In summary, we proposed a route to derivatives of scopine 3 amino 2 phenylpropionate via reactions of sco polamine hydrobromide with secondary amines. * Dedicated to Academician O. M. Nefedov on the occasion of his 75th birthday. Scheme 1

Sheets of π-stacked centrosymmetric molecules inN,N′-bis(3-nitrobenzylidene)octane-1,8-diamine

In mol­ecules of the title compound, C22H26N4O4, which lie across centres of inversion, the central octane fragment adopts a nearly planar all-trans conformation. There are no hydrogen bonds in the crystal structure but the mol­ecules are linked into sheets by a single π–π stacking inter­action.

ChemInform Abstract: Synthesis of a New Heterocyclic System Containing a 1,4‐Diazabicyclo(2. 2.2)octane Fragment.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Versatile Syntheses of Alkynyl- and Substituted Alkynylcyclopropanes: 2-Alkoxyethynylcyclopropanes for the Anellation of Bicyclo[3.3.0]octane Fragments

Enol ethers 1a-f are brominated at - 78° C and the resulting alkyl 1,2-dibromoethyl ethers are regioselectively coupled with propargyl-magnesium bromide to give 4-alkoxy-5-bromo-1-pentynes 2a-f, which are protected at the acetylenic terminus with a trimethylsilyl group. These 4-alkoxy-5-bromo-1-trimethylsilyl-1-pentynes 3a-f readily cyclize by γ-elimination to give trimethylsilyl protected 2-alkoxyethynylcyclopropanes 4a-f in excellent overall yields. Under appropriate conditions (E)-diastereomers (E)-4a-f can be prepared selectively. The diastereoselectivity of the bromine addition onto enantiomerically pure chiral enol ethers 1e and 1f, however, is 64% (for 2f) at best. 2-Alkoxy-1-trimethylsilylethynyl-cyclopropanes (E/Z)-4 can be deprotonated with LDA or butyllithium to give configurationally stable 1-lithio derivatives (E)-6, which are trapped by reactive electrophiles (protons, carbonyl compounds, tosyl halides) with retention of configuration on the three-membered ring. 2-Alkoxy-1-ethynylcyclopropanes 5 can be used to anellate a bicyclo[3.3.0]octane fragment onto a cycloalkene in a domino-type reaction sequence, as demonstrated by the Pauson-Khand cycloaddition of (E)-5c to norbornene (14) as well as deltacyclene (20), and subsequent interconversion to the tetracyclic and hexacyclic compounds anti/syn-19 and anti/syn-25/27 with a reasonable degree of diastereoselectivity.

ChemInform Abstract: A Short Synthesis of Bi‐ and Tricyclic Compounds Containing a 3‐Oxabicyclo(3.3.0)octane Fragment from Conjugated Enynes via Successive AdE‐Reaction and (2 + 2 + 1)Cycloaddition.

ChemInform Abstract: A Short Synthesis of Bi‐ and Tricyclic Compounds Containing a 3‐Oxabicyclo(3.3.0)octane Fragment from Conjugated Enynes via Successive AdE‐Reaction and (2 + 2 + 1)Cycloaddition.

Short path to the synthesis of bi- and tricyclic compounds containing the 3-oxabicyclo[3.3.0]octene fragment from conjugated enynes by successive AdE reaction and [2+2+1]-cycloaddition

A short general scheme was developed for the synthesis of a series of bi- and tricyclic compounds containing a 3-oxa-bicyclo[3.3.0]octane fragment on the basis of the successive acylallyloxylation of the double bond in the hexacarbonyldicobalt complexes of conjugated enynes and subsequent intramolecular [2+2+1]-cycloaddition.

Analogues of prostacyclin (PGI2) modified in the 2-oxabicyclo[3.3.0]octane fragment (review)

A review is given of the synthetic analogs of the prostacyclins having greater chemical and metabolic stability than prostacyclin itself. Possible routes for synthesis are discussed.

ChemInform Abstract: REACTIONS OF PHOSPHORANES CONTAINING A 3,5,8‐TRIS(TRICHLOROMETHYL)‐1,4‐DIPHOSPHA‐2,6,7‐TRIOXABICYCLO(2.2.2)OCTANE FRAGMENT WITH ANILINE

Chemischer InformationsdienstVolume 15, Issue 4 Organoelement Compounds ChemInform Abstract: REACTIONS OF PHOSPHORANES CONTAINING A 3,5,8-TRIS(TRICHLOROMETHYL)-1,4-DIPHOSPHA-2,6,7-TRIOXABICYCLO(2.2.2)OCTANE FRAGMENT WITH ANILINE L. N. MARKOVSKII, L. N. MARKOVSKIISearch for more papers by this authorA. V. SOLOV'EV, A. V. SOLOV'EVSearch for more papers by this authorM. I. POVOLOTSKII, M. I. POVOLOTSKIISearch for more papers by this authorYU. G. SHERMOLOVICH, YU. G. SHERMOLOVICHSearch for more papers by this author L. N. MARKOVSKII, L. N. MARKOVSKIISearch for more papers by this authorA. V. SOLOV'EV, A. V. SOLOV'EVSearch for more papers by this authorM. I. POVOLOTSKII, M. I. POVOLOTSKIISearch for more papers by this authorYU. G. SHERMOLOVICH, YU. G. SHERMOLOVICHSearch for more papers by this author First published: January 24, 1984 https://doi.org/10.1002/chin.198404239Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue4January 24, 1984 RelatedInformation