David Cameron is to hold face-to-face talks with Iranian president Hasan Rouhani in a fresh bid to revive the stalled Syrian peace process.
The pair will sit down together on Tuesday in New York, where they are among world leaders attending a United Nations summit.
Efforts to engage Tehran - a close ally of Bashar Assad's regime in Syria - in a push to end the protracted civil war have been spurred on by a thaw in relations with the West.
Mr Cameron said he hoped to build on the summer signing of an international deal on Iran's nuclear programme to bolster regional support for a political settlement in Syria.
But he was accused by Labour leader Jeremy Corbyn of failing to show leadership on the issue by choosing not to address the main UN General Assembly session in person, leaving it to Foreign Secretary Philip Hammond to speak for the UK on Syria.
Mr Cameron is attending several sessions on issues such as climate change, peacekeeping and the fight against Islamic State, but will not join Mr Rouhani, US president Barack Obama, Russian president Vladimir Putin and China's Xi Jinping in making a keynote speech.
Mr Corbyn said: "The situation in Syria is desperate, with half the population displaced from their homes and 200,000 dead.
"What matters now is a broad and comprehensive plan as the foundation for a political solution to the conflict and a new United Nations Security Council resolution.
"That's why it is so disappointing that David Cameron isn't showing leadership and unlike other world leaders won't be speaking at the UN this week."
The conflict - which has cost more than 250,000 lives, left Europe struggling to deal with a huge influx of refugees and enabled the rise of Islamic State extremists - is set to dominate the annual UN General Assembly.
It comes amid concerns over an unexpected build-up of Russian troops in support of the Moscow-backed Assad regime - which the Kremlin says is the best way to take on IS, also known as Isil.
The Prime Minister will use one-to-one talks with a number of key figures - though not Mr Putin - to press his case that the Syrian president "can't be part" of a peaceful solution to the civil war.
But with Europe increasingly overwhelmed by the upsurge of refugees fleeing the conflict and IS in control of large swathes of the country, he has joined Western allies such as the US and France in signalling a willingness to discuss whether he could play a transitional role.
Speaking to reporters accompanying him on the visit - which will also focus on climate change and new UN development goals - Mr Cameron said it was about "stepping up" international efforts to take on the militant threat.
"Assad can't be part of Syria's future. He has butchered his own people. He has helped create this conflict and this migration crisis. He is one of the great recruiting sergeants for Isil," he said.
"He can't play a part in the future of Syria and that position hasn't changed.
"Obviously conversations about how we bring about transition are very important and that's what we need to see greater emphasis on."
Asked if he believed Assad should face prosecution at the International Criminal Court, he said: "People who break international law should be subject to international law."
Mr Cameron said Russia and other powers had to be persuaded that it was "in everyone's interests" to co-operate in the fight against IS.