Sustainable Process for Sparteine Sulfate Preparation

Abstract

(−)-Sparteine sulfate is a stable salt of the quinolizidine chiral diamine alkaloid (−)-sparteine. This compound, in addition to presenting various biological activities, has successfully been used as a ligand and organocatalyst in enantioselective lithiation reactions in asymmetric synthesis. (−)-Sparteine free base deteriorates gradually, even in refrigeration, but its stable salt, (−)-sparteine sulfate, offers advantages in handling and storage. To the best of our knowledge, no process exists in the literature for obtaining (−)-sparteine sulfate from the species of the plant genus Lupinus. In this work, we present an efficient and sustainable process to obtain (−)-sparteine sulfate and free base (−)-sparteine from leaves and stems of Lupinus montanus.

Metabolic engineering of narrow-leafed lupin for the production of enantiomerically pure (‒)-sparteine

“…Since the seeds of white lupin are consumed as snacks in Southern Europe upon alkaloid removal, chemists have developed methods for the chiral resolution of lupanine and its subsequent reduction to sparteine 17-19 . Interestingly, several wild North American lupins predominantly accumulate (−)-sparteine, including L. babiger 20 and L. montanus 21 . Outside the Lupinus genus, few species are known to display similar characteristics, in particular, scotch broom ( Cytisus scoparius , also known as Sarothamnus scoparius ) 22, 23 , which appears to have been the source of commercial (−)-sparteine throughout the 1990s and 2000s 4 .…”

“…Since the seeds of white lupin are consumed as snacks in Southern Europe upon alkaloid removal, chemists have developed methods for the chiral resolution of lupanine and its subsequent reduction to sparteine [17][18][19] . Interestingly, several wild North American lupins predominantly accumulate (−)-sparteine, including L. babiger 20 and L. montanus 21 .…”

Synthesis and Applications of the C2-Symmetrical Diamine 2,7-Diazabicyclo[4.4.1]undecane

“…TLC: R f = 0.58, EtOAc (KMnO 4 ). 1 Octahydro-1H-pyrrolo[1,2-a]azepin-8-amine (12). Bis-thiolactam 11 (0.1 g, 0.467 mmol, 1 equiv) was added to a flame-dried round-bottom flask under inert atmosphere.…”

“…11 Regla and co-workers recently reported a sustainable process for the isolation of the sulfate salt of 2. 12 The O'Brien laboratory has made elegant contributions to this field in the development of their (+)-sparteine surrogate 3 (Figure 1). Diamine 3, which lacks the D ring of sparteine, gives enantioselectivities equal and opposite to those of 2.…”

“…The Maulide laboratory has reported a method for the extraction and isolation of both enantiomers of sparteine . Regla and co-workers recently reported a sustainable process for the isolation of the sulfate salt of 2 . The O’Brien laboratory has made elegant contributions to this field in the development of their (+)-sparteine surrogate 3 (Figure ).…”