Conformational Analysis of Marine Polyhalogenated β-Chamigrenes Through Temperature-Dependent NMR Spectra

Temperature-dependent ¹H- and ¹³C-NMR spectra reveal that polyhalogenated marine β-chamigrenes or synthetic derivatives thereof which are trans-diequatorially, substituted at C(8) and C(9), such as rogiolol ((?)- 2 ), obtusol ((+)- 3 ), and their acetates (+)- 1 and (?)- 4 , undergo slow ring- A chair-chair inversion. Conformational equilibria and kinetics are investigated with the aid of synthetic model compounds and molecular-mechanics calculations. Thus, steric repulsions between Br_ax–C(2) and H_eq–C(7) are seen to disfavour thermodynamically conformers 1b , 2b , 3b , and 4b , which can only be detected through cross-saturation transfer, while additional steric repulsions between Me_ax–C(1) and OH_ax–C(3) make conformer 8b of obtusol epimer so scarcely populated that it can not be detected. In agreement, with (+)- 9 and (+)- 10 , which have a trigonal C(2), two conformers can be directly observed by NMR. The kinetic barriers, which are seen to arise mainly from steric repulsions between H_ax–C(14) and the axial H or halogen atoms at C(8) and C(10), are calculated and discussed with respect to well documented exocycliemethylidene-substituted cyclohexane(ene) systems. This helps to rationalize why in rogiolol acetate ((+)- 1 ) ring B is unusually inert towards Zn/Et₂O/AcOH which causes bromohydrine-group elimination from ring A.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-dependent NMR spectra inverted-chair and twist-boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

α-Chamigren-3-one (+) -8 bearing an axial CI-atom at C(8) exists as a largely dominant conformer with Me—C(5) at the envelope-shaped enone ring pointing away from CI_ax?C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by ¹H-NMR. In contrast, the α-chamigren-3-ols (+) -9 and (+) -10 , obtained from hydride reduction of (+) -8 , show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+) -9 ) conformation to avoid repulsions between Me?C(5) and CI_ax–C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+) -12 of (+) -9 where Me–C(5) is pushed away from CI_ax–C(8) in a ring-B chair similar to that of (+) -8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+) -8 , as in enone (+) -15 (Scheme 3), does not affect the conformation; but a pseudoaxial Br? C(2) experiences repulsive interactions with H_eq–C(7), as shown by the ¹H-NMR data of the isomeric enone (+) -16 where the ‘normal’-chair conformer Cβ -16 is in an equilibrium with the inverted chair conformer ICβ -16 (Scheme 3). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α-chamigrenes. This view is supported by the acid-induced isomerization of α-chamigrene (+) -9 (inverted chair) to β-chamigrene (+) -17 (‘normal’ chair; Scheme 4), the driving force being the lesser space requirement of CH₂?C(5) than of Me–C(5). This explains why β-chamigrenes are so common in nature.     

Conformational deformation of ring C in 14β-estra- 1,3,5(10) 15-tetraen-17-ones

High-field n.m.r. analysis of four 3-methoxy-14β-estra-1,3,5(10), 15-tetraen-17-ones provides evidence for conformational deformation of ring C to a twist-boat form in solution. These observations are supported by molecular mechanics (MM2) calculations, which predict that the ring C chair and ring C twist-boat conformers have similar steric energies, slightly favouring the latter. An X-ray crystal structure determination on 3-methoxy-14-methyl-14β-estra-1,3,5(10), 15-tetraen-17-one revealed that ring C does indeed adopt a twist-boat conformation in the solid state.     

8α,9α-Epoxy-7-oxoroyleanon,ein Diterpen-Epoxychinon aus einer abessinischen Plectranthus-Art (Labiatae)

8α,9α-Epoxy-7-oxoroleyanone, a Diterpenoid Epoxyquinone from an Abyssinian Plectranthus Species (Labiatae) Reexamination of the title plant, in additon to the previously identified abietanoid hydroxy-1,4-benzoquinones 1a, 1b, 1c, 1e, 1f, 1g , and 1h , yielded the known 7α-acetoxyroleanone ( = 7-O-acetylhorminone; 1d ) and the novel 8α, 9α-epoxy-7-oxoroyleanone ( 2a ). Spectroscopic methods, partial synthesis by epoxidation of 7-oxoroyleanone ( 1h ), and chiroptical correlation establish the structure 2a . Royleanone 2a is the first diterpenoid epoxyquinone isolated so far. Moreover, a detailed ¹³C-NMR analysis of the royleanones 1b, 1c, 1e, 1g , and 1h lead to the complete assignment of their spectra.     

Tordanone,un stéroïde replié avec une jonction de cycle A/B β-cis (5β) et B/C α-cis(8α)

Tordanone, a Twice Bent Steroid Structure with Ring A/B β-cis(5β)- and Ring B/C α-cis(8α)-Fused The 3β, 14α, 25-trihydroxy-5β, 8α-cholestan-6-one ( = tordanone; 4 ) has been prepared by stereospecific hydrogenation of 3β, 14α, 25-trihydroxy-5β-cholesta-7,22ξ-dien-6-one ( 5 ). This is the first stereospecific synthesis of a B/C cis-fused steroid belonging to the 5β, 8α -cholestane group with a H-atom at positions 5β (A/B cis-fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β-face where CH₃(18) at the C/D ring junction and H_β? C(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.     

α-D-Glycosyl-Substituted α,α-D-Trehaloses with (1 → 4)-Linkage: Syntheses and NMR Investigations

Two symmetrical trehalose glycosyl ‘acceptors’ 4 and 6 were prepared and three of the unsymmetrical type, 8 , 10 , and 11 . Glucosylation of symmetrical ‘acceptor’ 4 gave a higher yield of trisaccharide (44%) than protect ve-group manipulation, namely via selective debenzylidenation 2 → 9 or monoacetylation 2 → 5 which proceeded in moderate yields (33–34%). A comparison of catalysts in the cis-glucosylation of trehalose ‘acceptor’ 10 with tetra-O-benzyl-β-D -glucopyranosyl fluoride 13 profiled triflic anhydride ((Tf)₂O) as a new reactive promoter yielding 92% of trisaccharide 14 , deblocking gave the target saccharide α-D -glucopyranosyI-( 1 → 4 )-α,α-D -trehalose. ¹H-NMR spectra of most compounds were analyzed extensively. The use of the ID TOCSY technique is advocated for its time efficiency, if needed supplemented by ROESY experiments.     

Copolymer synthesis of poly(L-lactide-b-DMS-L-lactide) via the ring opening polymerization of L-lactide in the presence of α,ω-hydroxylpropyl-terminated PDMS macroinitiator

Various amounts of hydroxy terminated PDMS were linked into PLLA chains via in-situ ring opening polymerization at a very low content of SnOt₂. The ¹H and FTIR spectra provided evidence for the incorporation of the PDMS in the PLLA chains. The molecular weights, T_g, T_m, crystallinity and the heats of fusion decreased as the feed mole ratio of PDMS/LLA in the block copolymer increased. The molecular weight distribution broadened as the content of the PDMS increased, due the occurrence of two initiation and propagation mechanisms. Linking PDMS into the PLLA chains improved its thermal stability. © 1996 John Wiley & Sons, Inc.     

Asymmetric Induction at C(β) and C(α) of N-Enoylsultams by Organomagnesium 1,4-Addition/Enolate Trapping

The 1,4-addition of alkylmagnesium chlorides to conjugated N-enoylsultams and subsequent ‘enolate trapping’ with aq. NH₄Cl or MeI/hexamethylphosphoric triamide generated centers of asymmetry at C(β) and/or at C(α) with good to excellent π-face defferentiation as demonstrated by the conversions 1 → 2 , 1 → 4 , and 8 → 9 . This holds also for the regioselective 1,4-addition of EtMgC1 to a dienoylsultam ( 15 → 16 ). Reactive conformations 1 ^≠, 8 ^≠, 13 , and 14 are postulated in agreement with X-ray evidence which also served for the structure determination of the product 9j .     

Furopyridines. VIII. Molecular structure and two-dimensional NMR spectral assignment of 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline

This paper reports the two-dimensional nmr spectral assignment and the X-ray structural determination of 2,14-dimethyl-8β-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline V which was obtained from 7,10-dimethyl-2β-hydroxy-14-oxo-2,3-(methanoiminoethano)-3β,4β-(propano)-3,4,5,6,7,8-hexahydro-2H-pyrano[2,3-c]pyridine IV by isomerization with hydrochloric acid. Both the compounds IV and V afforded the same dimethiodide IV -2MeI, while the configurational isomer 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5α,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline III gave monomethiodide III -Mel. The structures of these methiodides were also confirmed by X-ray analysis.