A facile synthesis of an oxatricyclic trans-syn-trans-substituted oxepanyl framework

Manta, Eduardo; Scarone, Laura; Hernández, Gonzalo; Mariezcurrena, R. A.; Suescun, Leopoldo; Brito, Iván; Brouard, Ignacio; González, Maritza; Pérez, Ricardo; Martı́n, Julio D.

doi:10.1016/s0040-4039(97)01302-6

Cited by 11 publications

(4 citation statements)

References 9 publications

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“…With the hope that the ca. 140 CCDB examples represent a statistically meaningful quantity, one finds that about three-quarters of them fall into only 5 of the 13 conformational types: TBC (23%); TCC (19%); TCBtype-1 (18%); SCBtype-1 (12%) (a representative CCDB example is cited for each conformational type). The remaining conformations are present in lower amounts: SCC (9%); TCBtype-2 (6%); SCBtype-3 (5%); TCBtype-3 (3%); TCTC (3%); SBBtype-1 (ca.…”

Section: Resultsmentioning

confidence: 99%

cis-Cyclononene Conformational Families and a Crystallographic Example of a Skew-Chair−Boat Type-2 Conformation

et al. 2002

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Cyclononanes from the 7 low-energy conformational archetypal families (twist-boat[bond]chair, twist-chair[bond]boat, twist-chair[bond]chair, twist-chair[bond]twist-chair, skew-chair[bond]boat, skew-chair[bond]chair, and skew-boat[bond]boat) were transformed into 12 of 13 MM3 stochastically generated cis-cyclononenes. This was done by systematically converting single bond synclinal endocyclic torsion angles, one-at-a-time, into double-bond synperiplanar analogues, followed by geometry optimization [e.g. density functional theory B3LYP/6-31G(d)]. Torsion angles adjacent to the new double bond maintained their signs, while their magnitudes usually changed considerably to accommodate the new neighboring synperiplanar torsion angles. The six remaining torsion angles all maintained their signs and approximate magnitudes compared to corresponding values in the seven saturated parent structures. As a result, the same "twist"/"skew" conformational descriptors previously used for the saturated conformers can now also be applied to the corresponding unsaturated analogues. Three conformational families have multiple members (subtypes) in which the double bond is located at different positions on the same ring conformation. The solid-state structures of (+/-)-1-phenyl-1,3,4,5,6,7-hexahydro-2,6-benzoxazonine-6-carbonitrile (22) and (1RS,3SR)-1-phenyl-3-methyl-1,3,4,5,6,7-hexahydro-2,6-benzoxazonine-6-carbonitrile (23) were determined by single-crystal X-ray diffraction analysis. The asymmetric unit of the Ponemacr; unit cell for 22 contains two symmetry-unrelated molecules, both of which exhibit a skew-chair-boat (SCBtype-2) conformation identical to that found for crystalline 23. This subtype has yet to be found in the Cambridge Crystallographic DataBase. Crystal lattice packing considerations alone cannot explain the observation of the SCBtype-2 conformation since (1)H NMR spectroscopy shows the same conformational bias when the crystals are dissolved in CDCl(3).

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Section: Resultsmentioning

confidence: 99%

cis-Cyclononene Conformational Families and a Crystallographic Example of a Skew-Chair−Boat Type-2 Conformation

et al. 2002

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“…11 As an extension of this methodology in a two-directional way, we describe in Scheme 3 the synthesis of tetrol 33 (F-H fragment). The readily available oxatricyclic oxepanyl derivative 28 obtained from (E,E,Z)-cyclododecatriene (26) via double cyclization of the bis-allylstannane 27 14 was derivatized to tetraenes 29 and 30 and submitted to RCM using 1 as the catalyst. In these processes, two rings and two carbon-carbon double bonds are formed in a single step to yield the unsaturated bis-lactone 31 and bis-silyloxy ether 32, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…1 H NMR (500 MHz, CDCl 3 ): d = 4.73 (br t, J = 3.8 Hz, 1 H, H-7), 4. 2 H,3.99 (dddd,1 H,J = 2.0,3.0,9.4,9.4 Hz,, 3.95-3.91 (m, 1 H, H-4), 2.21 (ddd,2 H,J = 4.0,5.0,7.3 Hz,[2][3][4][5][6][7][8]2.05 (ddddd,1 H,J = 2.0,2.3,7.3,7.3,14.0 Hz, H-9), 1.69 (br ddd, 1 H, J = 8.0, 8.0, 14.0 Hz, H-9), 1.39 (s, 3 H, CH 3 -2), 1.34 (s,3 H,. 13 C NMR (125 MHz, CDCl 3 ): d = 149.1 (C q , C 6 ), 118.5 (q, J = 320 Hz, CF 3 ), 109.9 (C q , C 2 ), 88.4 (CH, C 7 ), 80.2 (CH, C 9a ), 75.3 (CH, C 4a ), 66.8 (CH 2 , C 4 ), 26.7 (CH 3 , CH 3 -2), 25.0 (CH 3 , CH 3 -2), 23.1 (CH 2 , C 9 ), 18.9 (CH 2 , C 8 ).…”

Section: Lactone Derived Enol Triflate 42mentioning

confidence: 99%

Some Applications of Ring-Closing Metathesis to the Synthesis of trans-Fused Oxepane Polyethers

Brouard¹,

Liu²,

Martı́n³

2000

Synthesis

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“…The approach involves the application of β-hydroxyamide cyclodehydration methodologies toward the preparation of the oxazole fragment, [6] in combination with electrophilic oxirane expansion strategies for the construction of the cyclic ether moiety. [7] Since the three-dimensional (3D) structure and biological activity of these flexible molecules are intimately related, a priori knowledge of their conformational preferences in solution could be of critical importance in both the design and synthesis of analogs with phorboxazole-like cytostatic properties.…”

Section: Introductionmentioning

confidence: 99%

Conformational analysis of phorboxazole bis‐oxazole oxane fragment analogs by NMR spectroscopy and molecular modeling simulations

Fontana

Incerti

Moyna

et al. 2007

Magnetic Reson in Chemistry

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We present a detailed conformational study of a simplified synthetic analog of the bis-oxazole oxane fragment found in the cytostatic agents phorboxazole A and B based on results from NMR spectroscopy and molecular modeling simulations. Complete 1H and 13C resonance assignments for the bis-oxazole oxane system were carried out through the use of COSY, HSQC, HMBC, TOCSY, and HSQC-TOCSY experiments, and its conformational preferences in solution were investigated by analysis of 3J(HH) coupling constants and NOE enhancements obtained from 1D and 2D NOESY experiments. In order to solve inconsistencies from our preliminary structural studies, simulated annealing studies were performed to thoroughly sample the phase space available to the molecule. Our results reveal that the six-membered oxane ring, which constitutes the most important moiety regarding the three-dimensional (3D) structure and flexibility of the analog, exists in rapid equilibrium between its two accessible chair conformers in an approximate ratio of 70:30. The information gathered from these studies will be of critical importance in our efforts to prepare novel compounds with phorboxazole-like structure and activity.

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A facile synthesis of an oxatricyclic trans-syn-trans-substituted oxepanyl framework

Cited by 11 publications

References 9 publications

cis-Cyclononene Conformational Families and a Crystallographic Example of a Skew-Chair−Boat Type-2 Conformation

cis-Cyclononene Conformational Families and a Crystallographic Example of a Skew-Chair−Boat Type-2 Conformation

Some Applications of Ring-Closing Metathesis to the Synthesis of trans-Fused Oxepane Polyethers

Conformational analysis of phorboxazole bis‐oxazole oxane fragment analogs by NMR spectroscopy and molecular modeling simulations

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