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Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

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Chemistry of Opioids

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 299))

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Abbreviations

Ac:

Acetyl

acac:

Acetylacetonate

AIBN:

2,2′-Azobisisobutyronitrile

Ar:

Aryl

BINAP:

2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene

Bn:

Benzyl

Boc:

tert-Butoxycarbonyl

BOM:

Benzyloxymethyl

Bu:

Butyl

Bz:

Benzoyl

cat:

Catalyst

CC:

cis-cis

CDMT:

2-Chloro-4,6-dimethoxy-1,3,5-triazine

CNS:

Central nervous system

Cp:

Cyclopentadienyl

CT:

cis-trans

d:

Day(s)

dba:

Dibenzylideneacetone

DBAD:

Di-tert-butylazodicarboxylate

DBU:

1,8-Diazabicyclo[5.4.0]undec-7-ene

DCC:

N,N-Dicyclohexylcarbodiimide

DDQ:

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

DEAD:

Diethyl azodicarboxylate

DIAD:

Diisopropyl azodicarboxylate

DIBALH:

Diisobutylaluminum hydride

DMAP:

4-(Dimethylamino)pyridine

DMF:

Dimethylformamide

DMPU:

1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

DMSO:

Dimethylsulfoxide

DOB:

4-Bromo-2,5-dimethoxyamphetamine

DOP:

δ Opioid receptor

dppf:

1,1′-Bis(diphenylphosphino)ferrocene

EDCI:

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide

eq.:

Equivalent(s)

Et:

Ethyl

Fmoc:

9-Fluorenylmethoxycarbonyl

h:

Hour(s)

HOBt:

1-Hydroxybenzotriazole

HPLC:

High pressure liquid chromatography

Im:

Imidazole

i-Pr:

Isopropyl

KHMDS:

Potassium hexamethyldisilazide, potassium bis(trimethylsilyl)amide

KOP:

κ Opioid receptor

L:

Liter(s)

LAH:

Lithium aluminum hydride

LHMDS:

Lithium hexamethyldisilazide, lithium bis(trimethylsilyl)amide

LSD:

Lysergic acid diethylamide

m-CPBA:

m-Chloroperoxybenzoic acid

Me:

Methyl

MEM:

(2-Methoxyethoxy)methyl

Me-WMK:

(R)-(−)-Wieland–Miescher ketone

min:

Minute(s)

MNBA:

2-Methyl-6-nitrobenzoic anhydride

mol:

Mole(s)

MOM:

Methoxymethyl

MOP:

μ Opioid receptor

Ms:

Methanesulfonyl (mesyl)

NaHMDS:

Sodium hexamethyldisilazide

NBS:

N-Bromosuccinimide

n-bu:

n-Butyl

NCS:

N-Chlorosuccinimide

NMM:

4-Methylmorpholine

NMO:

4-Methylmorpholine N-oxide

PCC:

Pyridinium chlorochromate

PDC:

Pyridinium dichromate

Ph:

Phenyl

PPTS:

Pyridinium p-toluenesulfonate

Pr:

Propyl

PTSA:

p-Toluene sulfonic acid

Pv:

Pivaloyl

py:

Pyridine

rt:

Room temperature

s:

Second(s)

SAR:

Structure-activity relationship

s-Bu:

sec-Butyl

TBAF:

Tetrabutylammonium fluoride

TBS:

tert-Butyldimethylsilyl

TBSOTf:

tert-Butyldimethylsilyl trifluoromethaneulfonate

t-Bu:

tert-Butyl

TC:

trans-cis

TES:

Triethylsilyl

Tf:

Trifluoromethanesulfonyl (triflyl)

TFA:

Trifluoroacetic acid

TFAA:

Trifluoroacetic anhydride

THF:

Tetrahydrofuran

THP:

Tetrahydropyran-2-yl

TIPS:

Triisopropylsilyl

TLC:

Thin layer chromatography

TMS:

Trimethylsilyl

Tol:

4-Methylphenyl

Ts:

Tosyl, 4-toluenesulfonyl

TT:

trans-trans

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Acknowledgments

The authors thank the National Institute on Drug Abuse, the National Institutes of Health, and the University of Kansas for financial support of ongoing research programs. The content is the sole responsibility of the authors and does not necessarily represent the official view of the National Institute on Drug Abuse or the National Institutes of Health. K.M.L. and K.M.S. thank the NIH Dynamic Aspects of Chemical Biology Training Grant for pre-doctoral fellowships.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS, 66045-7582, USA

    Kimberly M. Lovell, Katherine M. Prevatt-Smith & Thomas E. Prisinzano

  2. Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA, 52242-1112, USA

    Anthony Lozama

Authors
  1. Kimberly M. Lovell
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  2. Katherine M. Prevatt-Smith
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  4. Thomas E. Prisinzano
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Correspondence to Thomas E. Prisinzano .

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Editors and Affiliations

  1. School of Pharmaceutical Sciences, Dept. Medicinal Chemistry, Kitasato University, Sirokane 5-9-1, Tokyo, 108-8641, Japan

    Hiroshi Nagase

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Lovell, K.M., Prevatt-Smith, K.M., Lozama, A., Prisinzano, T.E. (2010). Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects. In: Nagase, H. (eds) Chemistry of Opioids. Topics in Current Chemistry, vol 299. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2010_82

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