Modular Approach to Replication for Availability

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

10.26434/chemrxiv.7553444.v1 ◽

2019 ◽

Author(s):

Victor Bloemendal ◽

Floris P. J. T. Rutjes ◽

Thomas J. Boltje ◽

Daan Sondag ◽

Hidde Elferink ◽

...

Keyword(s):

Biological Activity ◽

Late Stage ◽

Medicinal Chemistry ◽

Cross Coupling ◽

Modular Approach ◽

Coupling Reactions ◽

One Pot ◽

Biologically Relevant ◽

Cross Coupling Reactions ◽

Chemistry Research

In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-trans-Δ8-THC derivatives, which can be used to modulate the pharmacologically important CB1 and CB2 receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ8-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.

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The Total Synthesis of Rhabdastrellic Acid A

10.26434/chemrxiv.7479944 ◽

2018 ◽

Author(s):

Yaroslav Boyko ◽

Christopher Huck ◽

David Sarlah

Keyword(s):

Total Synthesis ◽

Late Stage ◽

Cross Coupling ◽

Side Chains ◽

General Strategy ◽

Modular Approach ◽

Linear Sequence ◽

Generating Sequence ◽

First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained trans-syn-trans-perhydrobenz[e]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a p-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

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A Modular Approach to Protein Design

10.21236/ada220926 ◽

1990 ◽

Author(s):

H. N. Bramson

Keyword(s):

Protein Design ◽

Modular Approach

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The Staging of Large Wastewater Treatment Plants - A “Modular” Approach

Water Science & Technology ◽

10.2166/wst.1992.0482 ◽

1992 ◽

Vol 25 (4-5) ◽

pp. 67-73

Author(s):

H. Fleckseder ◽

L. Prendl ◽

H. Meulenbroek

Keyword(s):

Wastewater Treatment ◽

Driving Force ◽

Wastewater Treatment Plants ◽

Aeration Tank ◽

Modular Approach ◽

Central European ◽

Plant Hydraulics ◽

The World ◽

Whole Life Cycle ◽

Over Time

The primary driving force for re-investments in wastewater treatment plants in Austria - and also other countries in Central Europe - is at present not an increase in load to treatment but a marked increase in effluent requirements to be fulfilled. (The re-investments necessary for sludge handling and treatment remain outside this paper.) Within a period of 20 years, the load specific requirements on aeration tank volume rose five- to tenfold, when Lv = 2.0 kg BOD5/(m3d) was the starting value, and roughly doubled for final clarifiers. In addition, the importance of the application and expansion of primary sedimentation decreased as well. This development over time in Central European countries as well as the need to utilize previous investments as long as possible - 35 to 60 years for civil works are common as periods of depreciation - indicate that investments in new plant at any location in the world have to consider the possible whole life cycle of a plant and that plant hydraulics becomes the “key hook” for expandability.

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Design of Psycho-Pedagogical Cycle of Subjects, Taking Into Account the FSES: A Modular Approach

Tyumen State University Herald Humanities Research Humanitates ◽

10.21684/2411-197x-2016-2-4-235-245 ◽

2016 ◽

Vol 2 (4) ◽

pp. 235-245

Author(s):

Evgenia V. Korotayeva ◽

Anna S. Andryunina

Keyword(s):

Modular Approach

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Annex 1

10.1093/oso/9780198799931.003.0009 ◽

2018 ◽

Author(s):

Mokal et

Keyword(s):

Modular Approach ◽

Three Stages ◽

Implementation Stage

This first annex presents a basic checklist of steps that should be completed to implement reform that incorporates the Modular Approach. The process should have three stages, all of them complementary, each of them with less value if considered individually. They should follow a predefined order. The first part of the sequence would be to conduct an assessment. Second, and based on the results of the assessment, a drafting stage would be initiated. Third, following approval of the reform, an implementation stage would be commenced. Each part of the process is equally important, and, surprising as it might be, the seemingly more ancillary stages (assessment and implementation) usually take longer and require the most resources.

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Complementary Tools and Incentives

10.1093/oso/9780198799931.003.0005 ◽

2018 ◽

Author(s):

Mokal et

Keyword(s):

Modular Approach ◽

Insolvency Law ◽

Financial Situation ◽

Legal Advice ◽

Effective Use

This chapter discusses the complementary tools and incentives that can be adopted by jurisdictions to ensure the proper and effective use of the Modular Approach and to give due regard to the position and role of the various types of stakeholders involved in a MSME insolvency process. It specifically focuses on the roles and obligations of the MSME entrepreneur, both at times approaching insolvency and during the MSME insolvency process. Entrepreneurs do not always possess the education and skills to monitor the financial situation of their business and to react accordingly. With regard to the MSME framework, they would usually not be capable of designing a proper continuation plan. They might not even be aware that there is a chance to turn their business around by using mechanisms under insolvency law. In all these areas, education is a useful remedy. Jurisdictions should establish a method for providing affordable educational counselling and legal advice.

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