Pentacyclic System Research Articles

Synthetic Approach to Hypoxyxylerone, Novel Inhibitor of Topoisomerase I.

A potential route to the topoisomerase I inhibitor hypoxyxylerone is demonstrated by a highly convergent synthesis of the penta(O-methyl) derivative. The key step in the approach is an anionic homo-Fries rearrangement, little used to date in natural product synthesis and employed here for the first time with a dinaphthalenic substrate, to access the pentacyclic system of hypoxyxylerone.

Synthetic approach to hypoxyxylerone, novel inhibitor of topoisomerase I.

[reaction: see text] A potential route to the topoisomerase I inhibitor hypoxyxylerone is demonstrated by a highly convergent synthesis of the penta(O-methyl) derivative. The key step in the approach is an anionic homo-Fries rearrangement, little used to date in natural product synthesis and employed here for the first time with a dinaphthalenic substrate, to access the pentacyclic system of hypoxyxylerone.

A novel bridged hexahydropyrrolo[2,3-d]carbazole

The title compound, C22H26N2O2S2, consists of a pentacyclic system containing a carbazolenine skeleton with an ethyl group, a methoxy­ethyl group and a di­thiol­ane ring as substituents. A few interatomic close contacts seem to influence the geometry of the carbazolenine core structure.

One-step assembling reaction to the pentacyclic acetal of pinnatoxins

Treatment of acyclic tetraketone 8 with HF·py in MeCN afforded the pentacyclic system 1 in pinnatoxins with a high selectivity in good yield.

Cycloaddition-mediated strategies for synthesis of perhydrobenzo[14,15]-14β-19-norsteroids

Methods are described for sequential cycloaddition–fragmentation–recombination and cycloaddition–rearrangement-mediated processes for synthesis of the title compounds. Reaction of methyl vinyl ketone with 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate 1 gives a cycloadduct 2, which undergoes retroaldol cleavage followed by intramolecular Michael reaction, to generate 3-methoxy-5′,6′-dihydro-15αH-benzo[14,15]-14β-estra-1,3,5(10)-triene-4′(3′H),17-dione 4. Similarly, it is shown that various 16α-alkenyl-14α,17α-ethenoestradiols undergo ready [3,3]-sigmatropic rearrangement to give functional variants of this pentacyclic system. Synthetic routes to novel (perhydrobenzo)[14,15]-14β-analogues of estradiol are described, and aspects of the chemistry of 14β,16β-propano-19-norsteroids derived from alternative intramolecular reaction pathways are outlined.

The synthesis of new heterocyclic bridged ring systems. Analogs of tetrahydro-β-carbolines

New bridged β-carbolines were synthesized via a short synthetic route. The key step of the sequence is a Pictet-Spengler condensation under neutral conditions, employing a cyclic amine and several aldehydes. Using 5,5-diethoxypentanal gave a bridged analog which could be further ring closed to a new pentacyclic system.

Stereocontrol in the intramolecular Buchner reaction of diazoketones

Rhodium(II) acetate catalysed intramolecular Buchner cyclisation of a series of diazoketones 1 proceeds with excellent diastereoselectivity to produce the trans substituted azulenones 2, which exist as a rapidly equilibrating cycloheptatriene–norcaradiene system, from which the norcaradiene tautomers can be efficiently trapped as PTAD cycloadducts 4. The cyclisation–cycloaddition sequence can be conducted in either a stepwise or a tandem process, leading to the pentacyclic systems 4 as a single diastereomer in each case. In the reaction of diazoketone 1f intramolecular cyclopropanation competes with cyclisation to the aromatic ring.

Contribution to the Chemistry of Boron, 240 . Studies on Benzo‐1,3,2‐diphosphaborolanes, Benzo‐1,4,2,3‐diphosphadiborinanes and Benzo‐1,5,2,3,4‐diphosphatriborepanes

AbstractA series of benzo‐ 1,3,3‐diphosphaborolanes C6H4(PR)2BR' (R = H, iPr, SiMe3; R' = R2N, R) has been prepared by several routes and characterized by spectroscopic and – in part – by X‐ray diffraction methods. They feature pyramidal P atoms with the substituents in antiperiplanar positions. The P atoms act as coordination sites for the (CO)5Cr fragment. In contrast to the R2N‐bearing benzo‐1,3,2‐diphosphaborolanes, the derivative C6H4(PH)2BCMe3 (4f) dimerizes by additional B–P bond formation to produce a pentacyclic system (4f)2. – The reaction of C6H4(PHNa)2 with B2(NMe2)2Cl2 in THF/hexane yields the acyclic phosphanylborane Me2NB(PH–C6H4PH2)2 (15). However, if C6H4[P(iPr)Li]2 is allowed to react with B2(NMe2)2Cl2, the benzo‐1,4,2,3‐diphosphadiborinane 13 is obtained, together with its rearrangement product 2‐bis(dimethylamino)borylbenzo‐1,3,2‐diphosphaborolane 14 which dimerizes to (14)2. — In contrast, the almost planar ring of the 2,3‐dimesitylbenzo‐1,4,2,3‐diphosphadiborinane (16) possesses P and B atoms with a planar geometry. Short B–B and B–P bonds suggest that this new heterocycle can be regarded as a 6π electron system. Moreover, the benzo‐1,5,2,3,4‐diphosphatriborepane 18 forms readily forms readily from C6H4(PHNa)2 and Br(Me2N)B–B(N‐Me2)–B(NMe2) Br to give a tub‐shaped seven‐membered C2B3P2 ring system with the P atoms in a pyramidal and the B atoms in a planar environment.

Photochemical Experiments with 2,3‐Bis(Tert‐Butylsulfonyl)Bicyclo[2.2.2]Octa‐2,5‐Diene and Related Systems

AbstractThe irradiation of 2,3‐bis(tert‐butylsulfonyl)norbornadiene (5) and 2‐(tert‐butylsulfonyl)norbornadiene (6) yielded the expected quadricyclane derivatives as stable molecules. The irradiation of 2,3‐bis(tert‐butylsulfonyl)bicyclo[2.2.2]octa‐2,5‐diene(7) 2,3‐bis(tert‐butylsulfonyl)‐exo‐7,8‐epoxybicyclo[2.2.2]‐octa‐2,5‐diene (8) and 8,9‐bis(tert‐butylsulfonyl)‐4‐anti‐phenyl‐3,5‐dioxa‐exo‐tricyclo[5.2.2.02,6] undeca‐8,10‐diene 9a and its syn‐isomer 9b yielded the corresponding tetracyclic and pentacyclic systems, respectively. The photoproducts of 8 and 9 reverted to the starting products slowly at room temperature. The half‐life of the photoproduct of 7 was determined to be 34 min at 50 °C. Compound 9a reacted with n‐BuLi to yield the unexpected desulfonylation product 27a.

Organophosphorus Compounds; 104. Functionalization of a Pentacyclic Phosphorus-Carbon Cage Compound at Phosphorus

Depending on the reaction partners employed, the two phosphane functions in the pentacyclic cage compound 5 exhibit different reactivities. On reaction with alkyl halides (→ 8a-d) and o-benzoquinones (→ 17a-c), the expected increase in coordination at the all-carbon-substituted, more nucleophilic λ 3 σ 3-phosphorus atom P12 in the pentacyclic system 5 is observed to occur preferentially. Functionalizations with organic azides (Staudinger reaction, → 10a-c), tert-butyl hydroperoxide, cyclooctasulfur, and gray selenium (→ 13a-c), on the other hand, occur at the oxygen-substituted, more electrophilic λ 3 σ 3-phosphorus atom P2. In addition to electronic factors, steric interactions are implicated in the interpretation of the regiochemistry. The structure elucidations of the prepared derivatives of the cooligomeric cage compound 5 were based on NMR spectroscopic methods including selective irradiation and two-dimensional techniques. An X-ray crystal structure analysis of the phosphonium salt 8a has also been carried out.

A systematic NMR approach for the determination of the molecular structure of steroidal saponins.

Steroidal saponins and their aglycones (steroidal sapogenins), which are widely distributed in various plant families, are attracting the attention of research workers not only as economically important raw material convertible into various steroid hormonal drugs, but recently also as biologically active materials having independent value.1–6 All steroidal sapogenins possess a parent cholestane carbon skeleton (C27), having perhydrocyclopentenophenanthrene nucleus (rings A, B, C, and D), the side chain of which undergoes cyclization resulting in either a hexacyclic system (four carbocyclic and two heterocyclic rings) or a pentacyclic system (four carbocyclic and one heterocyclic ring). Most of these contain, in addition, one 5-membered ring (E) and one 6- or 5-membered ring (F), both of which are heterocyclic and fixed in a spiran fashion at C-22. Those cholestane derivatives which are formed by the ring opening of both heterocyclic rings are also included in this class because these have been regarded as intermediate in the biosynthesis of steroidal sapogenins.7–9

Excellent stereocontrol in intramolecular Buchner cyclisations and subsequent cycloadditions; stereospecific construction of polycyclic systems

Highly diastereoselective rhodium(II) acetate-catalysed intramolecular addition of α-diazo ketones to aromatic rings to form the azulenones 3 has been achieved; the norcaradiene form of 3 undergoes efficient stereospecific cycloaddition with phenyltriazolinedione, in either a stepwise or a tandem process, leading to the pentacyclic systems 4 as a single diastereomer in each case.

Total Synthesis of Brevetoxin B. 1. First Generation Strategies and New Approaches to Oxepane Systems

The fust generation strategies toward the total synthesis of brevetoxin B (1) are presented and the syntheses of the key intermediates 3, 4, 5, 67, 83, and 94-98 required for the projected construction are described. The earliest and most convergent strategy required the application of the hydroxy epoxide cyclization and the intramolecular conjugate addition as key reactions for the construction of the fused tetrahydropyran ring systems (4) [ABC], (7) [FG], and (8) [UK]. The oxocene ring (H) was formed via a Wittig reaction followed by a hydroxy dithioketal cyclization to produce the hexacyclic fragment [FGHIJK] (6 5). The 12-membered dithionolactone 18 was envisioned as the precursor of the dioxepane system of the molecule via a projected bridging reaction, to construct simultaneously both oxepane rings. However, the dithionation of dilactone 17 proved unsuccessful. In a subsequently evolved strategy, a new photolytic approach toward the dioxepane region was developed, starting from the acyclic dithiono progenitor 20 (20 23). Application of this reaction to the brevetoxin B skeleton afforded the desired oxepene (96 97), which after deprotection produced oxepanone 98. A specifically designed reductive hydroxy ketone cyclization (98 99) was then employed in an attempt to close the remaining ring [E], but, again, without success. The novel rearrangement of hydroxy ketone 87 to the pentacyclic system 89 was observed in a less elaborate skeleton. The scope and generality of these silicon-induced reductive cyclizations are also described.

SYNTHESIS OF A NEW PENTACYCLIC SYSTEM : PYRROLO[2,1-c]QUINAZOLlNO[3,2-a][1,4]BENZODIAZEPINES: ELUCIDATION OF STRUCTURES

Article SYNTHESIS OF A NEW PENTACYCLIC SYSTEM : PYRROLO[2,1-c]QUINAZOLlNO[3,2-a][1,4]BENZODIAZEPINES: ELUCIDATION OF STRUCTURES was published on October 1, 1995 in the journal Heterocyclic Communications (volume 1, issue 5-6).

Fused‐Skeleton Saturated Six‐Membered 1,3‐N,O, N,N and N,S Heterocycles. Fused‐Skeleton Aryl‐Substituted Saturated Isoindolones

AbstractIn the introduction, a brief survey is given of the main types of fused‐skeleton saturated six‐membered 1,3‐heterocycles serving as model compounds in our earlier investigations and as starting compounds in the present studies. The synthesis and conformational analysis of aryl‐substituted fused‐skeleton saturated 1,3‐oxazines and of aryl‐substituted hetero‐condensed saturated isoindolones are treated. cis‐trans isomerization in the saturated isoindolone moiety of the resulting tricyclic, tetracyclic and pentacyclic systems is discussed in connection with the ring‐closure reactions of cis‐ and trans‐1,2‐disubstituted 1,2‐ and 1,3‐difunctional alicyclic compounds to give alicycle‐fused six‐membered 1,3‐heterocycles. The cycloaddition reactions of dihydro‐1,3 and 3,1‐oxazines and the conformations of the alicycle‐fused tetrahydrooxazine‐azetidinone derivatives obtained are presented. Methods are given for the preparation of saturated thiazolo‐ and thiazino[2,3‐b]quinazolinones. Unambiguous, mainly one‐pot syntheses for the preparation of 1,3‐heterocycles by a retro Diels‐Alder method are discussed.

Synthesis and structure of new families of potential antitumor or antiviral agents. I. 4b,6a,10b,10c-Tetrahydrobenzo[3,4]cyclobuta[1,2-a]biphenylene-4b,6a-diyl diacetate

The bent triphenylene derivative 4b,6a,10b,10c-tetrahydrobenzo[3,4]cyclobuta[1,2-a]biphenylene-4b,6a-diyl diacetate was prepared during the course of research into the synthesis of aromatic polycyclic derivatives showing antitumor or antiviral activity, and its structure determined by X-ray diffraction. The two benzocyclobutene groups are and across the central cyclohexene ring; the acetoxy groups are anti to each other and cis to the benzocyclobutene groups. The geometry of the pentacyclic system is discussed and the factors determining the orientation of the acetoxy substituents are considered. The results of the refinements on F and F 2 are compared

A short Synthesis of (±) N-benzyl aspidospermiden

(±) N-benzyl aspidospermideine is synthesized in seven steps via the trisubstituted hexahydrocarbazolone 4, reductive cyclization of this intermediate which is obtained photocyclization and Michael reaction with nitroethylene, creates simultaneously both E and D rings of the pentacyclic system.

From Phosphaalkynes to Phosphacubanes — Adventures in Organophosphorus Chemistry[1]

AbstractPhosphaalkynes (4) — readily accessible from carboxylic acid chlorides and tris(trimethylsilyl)phosphane — serve as starting materials for the synthesis of phosphirenes (13, 18, 41, 45). The significance of the 1‐chloro‐2‐phosphirene (18) for the generation of phosphirenylium cations (A⟷B or C) as well as its ring enlargement reaction to 1,2‐dihydro‐1,2‐phosphasilete (28) and its ring cleavage reaction to 1,2,3‐butatrienes (48) and vinylallenes (51) are illustrated. The non‐selective thermal cyclotetramerization of 4 to give, among others, the tetraphosphacubane 56 is compared with a preparative, two‐step procedure starting from the tricyclic zirconium complex 60; the latter process provides higher yields of 56. The phosphorus atoms in the pentacyclic system can be functionalized by a wide range (66–73). In the presence of Lewis acids such as aluminium trichloride, phosphaalkynes (4) undergo spirocyclotrimerization to furnish betaines of the type 77.

A new strategy for the enantioselective synthesis of aspidosperma alkaloids: II - Achievement of the pentacyclic system.

Carbazolone 5 has been converted in eleven steps into alkaloid analog 1 (R = Me) (13% overall yield).

ChemInform Abstract: Stereospecific Synthesis of the Cyclopenta(e)phenanthridine Ring System: Tetracyclic and Pentacyclic Analogues of Cephalotaxus Alkaloids.

Abstract Methylenedioxy- and dimethoxy-derivatives of the hexahydrocyclopenta[e]phenanthridine ring system. (21a) and (21b), have been synthesised stereospecifically in six steps starting from piperonal (50% overall yield) and dimethoxybenzaldehyde (27% overall yield), respectively. Piperonal was converted into nitrostyrene derivative (13a) by the known procedure; compound (13a) on reaction with butadiene sulphone afforded the butadiene cycloaddition product (14a) which reacted with methyl acrylate in base to yield nitro-ester (15a) in a stereospecific Michael addition. Reductive cyclisation of compound (15a) using zinc and hydrochloric acid gave spirolactam (16a) which was reduced with lithium aluminium hydride to yield spiropyrrolidine (18a); this compound was converted into the pentacyclic system (21a) by reaction with formaldehyde under Pictet-Spengler conditions. Thiolactam (17a), was obtained from reaction of lactam (16a) and phosphorus pentasulphide, and was methylated with methyl iodide to give lactlminium salt (19a) which reacted with sodium borohydride to yield thiolactim derivative (20a). The route to tetracyclic compound (21b) directly paralleled this sequence.