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Total Synthesis of HUN-7293
No full textThe first total synthesis of the cyclic heptadepsipeptide HUN-7293 (1), a potent inhibitor of cell
adhesion molecule expression exhibiting anti-inflammatory properties, is detailed. The most effective approach
relied on an unusually efficient macrocyclization with the formation of the MLEU3−LEU4 secondary amide
that potentially benefits from intramolecular H-bonding preorganization of the acyclic substrate. The requisite
linear depsipeptide was convergently assembled with the late stage introduction of the linking ester enlisting
a Mitsunobu esterification that occurs with inversion of the DGCN α-center permitting the utilization of a
readily available l-amino acid precursor to the d α-hydroxy carboxylic acid residue. An alternative and similarly
attractive approach of direct macrolactonization of a substrate necessarily incorporating a d-DGCN subunit
proved viable albeit less effective. Biological evaluation in cellular assays for vascular adhesion molecule
expression confirmed that synthetic HUN-7923 (1) is essentially indistinguishable from the naturally occurring
cyclodepsipeptide
A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293
No full textA two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been
developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid
methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy
acid amides under smooth conditions. Successful application of this methodology to the open-chain
transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent
inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide
18 with unprotected N-terminus in 70−75% yield. This result demonstrates that the protocol
developed even works in the presence of an ester and several methylated and unmethylated amide
bonds. Finally, a sequence of ligation of methyl d-dehydroglutaminate (20) to the C-terminus of
the saponification product 21, followed by the degradation protocol and ring closure, allowed
chemical “point mutation” at the DGCN site affording the aza analogue of HUN-7293 (24) in 15%
overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of
2-hydroxy acid amides
A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293
No full textA two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been
developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid
methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy
acid amides under smooth conditions. Successful application of this methodology to the open-chain
transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent
inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide
18 with unprotected N-terminus in 70−75% yield. This result demonstrates that the protocol
developed even works in the presence of an ester and several methylated and unmethylated amide
bonds. Finally, a sequence of ligation of methyl d-dehydroglutaminate (20) to the C-terminus of
the saponification product 21, followed by the degradation protocol and ring closure, allowed
chemical “point mutation” at the DGCN site affording the aza analogue of HUN-7293 (24) in 15%
overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of
2-hydroxy acid amides
A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293
No full textA two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been
developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid
methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy
acid amides under smooth conditions. Successful application of this methodology to the open-chain
transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent
inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide
18 with unprotected N-terminus in 70−75% yield. This result demonstrates that the protocol
developed even works in the presence of an ester and several methylated and unmethylated amide
bonds. Finally, a sequence of ligation of methyl d-dehydroglutaminate (20) to the C-terminus of
the saponification product 21, followed by the degradation protocol and ring closure, allowed
chemical “point mutation” at the DGCN site affording the aza analogue of HUN-7293 (24) in 15%
overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of
2-hydroxy acid amides
A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293
No full textA two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been
developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid
methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy
acid amides under smooth conditions. Successful application of this methodology to the open-chain
transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent
inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide
18 with unprotected N-terminus in 70−75% yield. This result demonstrates that the protocol
developed even works in the presence of an ester and several methylated and unmethylated amide
bonds. Finally, a sequence of ligation of methyl d-dehydroglutaminate (20) to the C-terminus of
the saponification product 21, followed by the degradation protocol and ring closure, allowed
chemical “point mutation” at the DGCN site affording the aza analogue of HUN-7293 (24) in 15%
overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of
2-hydroxy acid amides
Envelope masses and distances to planetary nebulae: IC 5117 and NGC 7293
No full textРазработана методика самосогласованного определения массы Mi ионизованного газа в оболочках планетарных туманностей (ПТ) и расстояния D до них, основанная на расчете оптимизированных фотоионизационных моделей их свечения (ОФМС). Рассчитаны модели «молодой» туманности ІС 5117 и «старой» NGC 7293. Определены значения Mi= 0.0056M⊙ и D = 1287 пк для IC 5117 и Mi= 0.681M⊙ и D = 201 пк для NGC 7293 соответственно.Розроблено методику самоузгодженого визна чення маси Mi іонізованого газу в оболонках планетарних туман ностей (ПТ) і відстані D до них, основану на розрахунку оптимізованих фотоіонізаційних моде лей їхнього світіння (ОФМС). Разраховано моделі «молодої» туман ності ІС 5117 і «старої» NGC 7293. Визначено Mi= 0.0056M⊙ і D = 1287 пк для IC 5117 і Mi= 0.681M⊙ і D = 201 пк для NGC 7293 відповідно.Self-consistent method to determine the masses Mi of the ionized gas in envelopes of planetary nebulae (PNe) and the distances D to those ones is developed. The method is based on the calculation of optimized photoionization model (OPhM) of a planetary nebula envelope. Models of the «young» nebula IC5117 and «old» one NGC7293 are calculated. Correspondingly, the values of Mi and D for IC5117 (Mi= 0.0056M⊙, D = 1287 pc) and NGC7293 (Mi= 0.681M⊙, D = 201 pc) are determined
Envelope masses and distances to planetary nebulae: IC 5117 and NGC 7293
No full textРазработана методика самосогласованного определения массы Mi ионизованного газа в оболочках планетарных туманностей (ПТ) и расстояния D до них, основанная на расчете оптимизированных фотоионизационных моделей их свечения (ОФМС). Рассчитаны модели «молодой» туманности ІС 5117 и «старой» NGC 7293. Определены значения Mi= 0.0056M⊙ и D = 1287 пк для IC 5117 и Mi= 0.681M⊙ и D = 201 пк для NGC 7293 соответственно.Розроблено методику самоузгодженого визна чення маси Mi іонізованого газу в оболонках планетарних туман ностей (ПТ) і відстані D до них, основану на розрахунку оптимізованих фотоіонізаційних моде лей їхнього світіння (ОФМС). Разраховано моделі «молодої» туман ності ІС 5117 і «старої» NGC 7293. Визначено Mi= 0.0056M⊙ і D = 1287 пк для IC 5117 і Mi= 0.681M⊙ і D = 201 пк для NGC 7293 відповідно.Self-consistent method to determine the masses Mi of the ionized gas in envelopes of planetary nebulae (PNe) and the distances D to those ones is developed. The method is based on the calculation of optimized photoionization model (OPhM) of a planetary nebula envelope. Models of the «young» nebula IC5117 and «old» one NGC7293 are calculated. Correspondingly, the values of Mi and D for IC5117 (Mi= 0.0056M⊙, D = 1287 pc) and NGC7293 (Mi= 0.681M⊙, D = 201 pc) are determined
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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