(Z)-CAPSAICIN Chemical Properties

Melting point:

70 °C

Boiling point:

511.5±50.0 °C(Predicted)

Density 

1.041±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

pka

9.76±0.20(Predicted)

color 

White to Off-White

Stability:

Light Sensitive

Safety Information

Toxicity

LD50 intraperitoneal in mouse: 25mg/kg

(Z)-CAPSAICIN Usage And Synthesis

Description

Zucapsaicin is a topical analgesic that was approved in Canada in July 2010 for use in conjunction with oral COX-2 inhibitors or NSAIDs to relieve severe pain in adults with osteoarthritis of the knee. Zucapsaicin is the cis-isomer of the natural product capsaicin. Capsaicin is available without a prescription in creams, lotions, and patches for the treatment of neuropathic and musculoskeletal pain. Zucapsaicin is available as a 0.075% by weight cream. The advantages of zucapsaicin compared with capsaicin are reported to be a lesser degree of local irritation (stinging, burning, erythema) in patients and a greater degree of efficacy in preclinical animal models of pain. The analgesic action of zucapsaicin and capsaicin is mediated through the transient receptor potential vanilloid type 1 (TRPV1) channel.

Originator

E Merck AG (Germany)

Uses

(Z)-CAPSAICIN is used as a tool in neurobiological research. Prototype vanilloid receptor agonist.

Definition

ChEBI: Zucapsaicin is a member of phenols and a member of methoxybenzenes.

brand name

Civanex

Clinical Use

Zucapsaicin, the cis-isomer of the natural product capsaicin, is a topical analgesic that was initially developed by Winston Pharmaceuticals and approved in Canada in July 2010 for the treatment of severe pain in adults with osteoarthritis of the knee. The advantages of zucapsaicin compared with naturally-occurring capsaicin are reported to be a lesser degree of local irritation (stinging, burning, erythema) in patients and a greater degree of efficacy in preclinical animal models of pain. The analgesic action of both zucapsaicin and capsaicin is mediated through the transient receptor potential vanilloid type 1 (TRPV1) channel, a ligand-gated ion channel expressed in the spinal cord, brain, and localized on neurons in sensory projections to the skin, muscles, joints, and gut.

Synthesis

The scale preparation of zucapsaicin likely parallels the original approach described by Gannett and co-workers involving the coupling of vanillylamine with (Z)-8-methylnon-6-enoyl chloride. 216 Orito and co-workers elaborated this original approach in an effort to prepare both capsaicin and zucapsaicin on gram-scale, and this route is described in the scheme.

Commercial 6-bromohexanoic acid (285) was activated as the Wittig salt prior to condensation with isobutylaldehyde in the presence of strong base to generate an 11:1 ratio of E/Z-olefinic acids favoring Z-isomer 286. Removal of the minor isomer was easily achieved by short-path distillation.217 Interestingly, the authors reported that facile olefin isomerization of 286 occurred upon exposure to nitric acid at elevated temperatures, converting 286 to the corresponding E-isomer. Recrystallization provided the product on multi-gram scale in 77% yield, representing a possible scale production method for capsaicin. For the preparation of zucapsaicin, acid 286 was converted the acid chloride via thionyl chloride followed by immediate condensation with commercially available vanillylamine (287). Two recrystallization steps were subsequently employed to produce gram-scale amounts of zucapsaicin (XXVI) in 66% yield overall for the two-step process.

(Z)-CAPSAICIN(25775-90-0)Related Product Information

• Nonivamide
• Z-VAD-FMK
• ZSTK474
• Z-Vad-fmk, non-methylated
• ZT-12-037-01
• (E)-CAPSAICIN,CAPSAICIN, NATURAL
• (Z)-CAPSAICIN
• Capsaicin pure,capsaicin(fromoleoresinofcapsicum)plusrelatedcapsaicinoid
• Capsicumoleoresin/Capsaicin,10%,Capsicumoleoresin/Capsaicin,6.2%,Capsicumoleoresin/Capsaicin,3.3%
• 1-NONENE
• Capsaicin-D3
• Anti-Capsaicin Receptor (Ab-1), Rat (Rabbit)
• CAPSAICIN, EMULSION LIGUID
• CAPSAICIN RECEPTOR (AB-1) POLYCLONAL ANTIBODY
• CAPSAICIN [14C]
• CAPSAICIN, NATURAL SOLUTION 100UG/ML IN TOLUENE 1ML
• CAPSAICIN, NATURAL 100MG [R]
• N-VANILLYLNONANAMIDE (SYNTHETIC CAPSAICIN) = N-[94-HYDROXY-3-METHOXYPHENYL)METHYL]NONANAMIDE